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Sun Y, Zhang J, Zhang L, Qiu L, Zhang H. Clinical value of microRNA-4449 of non-small cell lung cancer patients undergoing thoracic paravertebral block thoracotomy. Mol Cell Probes 2025; 80:102020. [PMID: 39984060 DOI: 10.1016/j.mcp.2025.102020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 01/01/2025] [Accepted: 02/19/2025] [Indexed: 02/23/2025]
Abstract
OBJECTIVE The aim of this study was to investigate the clinical significance of microRNA-4449 (miR-4449) in patients attacked by non-small cell lung cancer (NSCLC) undergoing thoracic paravertebral block (TPVB) thoracotomy. METHODS A total of 122 patients diagnosed with NSCLC and 101 healthy individuals were recruited in this case-control study. Quantitative real-time polymerase reaction time (qRT-PCR) assay was applied to quantify the serum levels of miR-4449 in all participants. To assess the diagnostic potential of miR-4449, receiver operating characteristic (ROC) curves were constructed. Additionally, the prognostic value of miR-4449 was evaluated using Kaplan-Meier method and Cox regression analyses. The possible target genes and related proteins of miR-4449 were predicted via bioinformatics analysis. RESULTS MiR-4449 expression was notably reduced in NSCLC patients relative to healthy volunteers (P < 0.001), with the area under the curve (AUC) reaching 0.952, demonstrating its ability to effectively differentiate between NSCLC patients and healthy individuals. Serum levels of miR-4449 were negatively in relation to tumor node metastasis stage and lymph node metastasis (P < 0.05). Moreover, a significant increase in miR-4449 expression was observed in patients following TPVB thoracotomy, as compared to pre-operative levels (P < 0.001). The AUC of 0.884 further highlighted its potential to distinguish between the effective group and the invalid group. Notably, patients expressing high levels of miR-4449 exhibited improved overall survival (P < 0.001), and miR-4449 (P < 0.001, HR = 2.290, 95 % = 1.450-3.615) was identified as an independently prognostic predictor for NSCLC. Bioinformatics analysis of miR-4999 target genes revealed key tumor-associated pathways and proteins, offering valuable insights into its molecular mechanisms in NSCLC. CONCLUSION Serum levels of miR-4449 were significantly decreased in patients with NSCLC and exhibited a correlation with the severity of the tumor. Furthermore, miR-4449 emerged as a potential prognostic biomarker, offering valuable insight into the clinical outcome for NSCLC undergoing TPVB thoracotomy.
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Affiliation(s)
- Yu Sun
- Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Jiantao Zhang
- Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, China; Qingdao University, Qingdao, 266071, China
| | - Licai Zhang
- Department of Anesthesiology, Zigong Fourth People's Hospital, Zigong, 643000, China
| | - Liquan Qiu
- Department of Anesthesiology, Zigong Fourth People's Hospital, Zigong, 643000, China.
| | - Huayi Zhang
- Department of Radiation Oncology, The First People's Hospital of Yongkang, Jinhua 321300, China.
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2
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Sinha A, Sra M, Ahmed A, Mallick S, Saini H, Devi KG, Hari P, Bagga A. MicroRNAs in idiopathic childhood nephrotic syndrome. Clin Exp Nephrol 2025; 29:477-484. [PMID: 39630311 DOI: 10.1007/s10157-024-02595-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 11/08/2024] [Indexed: 03/26/2025]
Abstract
BACKGROUND miRNAs are non-coding RNA that are recognized as biomarkers of kidney disorders. There is limited information on the differential expression of miRNA and their target genes in idiopathic nephrotic syndrome of childhood. METHODS We enrolled patients, 2-18 years old, with steroid-sensitive nephrotic syndrome, either at onset or during relapse, and steroid-resistant disease, at diagnosis of steroid-resistance. Patients with steroid-sensitive disease were off immunosuppressive medications, while those with steroid-resistance were on therapy with prednisolone at enrollment. Controls were healthy children attending the hospital for vaccinations or for minor non-infectious, non-kidney ailments. Following RNA extraction from whole blood, differential expression of 2549 miRNAs was examined to identify differentially expressed miRNA, defined as those with absolute log2 fold change > 2 and adjusted P < 0.05. Target genes, predicted using miRNet, were compared against the genes for nephrotic syndrome in the NCBI database, and the ontology of selected genes was examined using DAVID. RESULTS Comparison of miRNA expression in 36 patients and 12 controls led to the identification of 62 and 12 differentially expressed miRNA in patients with steroid-sensitive and steroid-resistant disease, respectively. Of 76 miRNAs that were differentially regulated between the two disease categories, 26 were unique to steroid-sensitive disease and 11 to steroid-resistance. Of 5955 and 2813 genes targeted by the miRNAs specific to steroid-sensitive and steroid-resistant nephrotic syndrome, respectively, 79 were relevant in context of the disease. CONCLUSION Steroid-sensitive and steroid-resistant nephrotic syndrome have distinct miRNA expression profiles, which can be examined as biomarkers and in pathogenetic pathways.
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Affiliation(s)
- Aditi Sinha
- Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Manraj Sra
- Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Aijaz Ahmed
- Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Saumyaranjan Mallick
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Himanshi Saini
- Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Kshetrimayum Ghanapriya Devi
- Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Pankaj Hari
- Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Arvind Bagga
- Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.
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Hasan MDN, Rahman MM, Husna AA, Arif M, Jasineviciute I, Kato D, Nakagawa T, Miura N. Upregulation and functional roles of miR-450b in canine oral melanoma. Noncoding RNA Res 2024; 9:376-387. [PMID: 38511062 PMCID: PMC10950611 DOI: 10.1016/j.ncrna.2024.01.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/24/2024] [Accepted: 01/29/2024] [Indexed: 03/22/2024] Open
Abstract
Canine oral melanoma (COM) is a common and highly aggressive disease with the potential to model human melanomas. Dysregulated microRNAs represent an interesting line of research for COM because they are implicated in tumor progression. One example is miR-450b, which has been investigated for its molecular mechanisms and biological functions in multiple human cancers, but not human or canine melanoma. Here, we aimed to investigate miR-450b as a potential diagnostic biomarker of COM and its functional roles in metastatic and non-metastatic forms of the disease. We investigated the expression of miR-450b and its target mRNA genes in clinical (tumor tissue and plasma) samples and metastatic and primary-tumor cell lines. Knockdown and overexpression experiments were performed to determine the influence of miR-450b on cell proliferation, migration, colony formation, and apoptosis. miR-450b was significantly upregulated in COM and differentiated between metastatic and non-metastatic tumors, and its potential as a biomarker of metastatic and non-metastatic COM was further confirmed in ROC analysis. miR-450b knockdown promoted cell proliferation, migration, and clonogenicity and inhibited apoptosis, whereas its overexpression yielded the reverse pattern. miR-450b directly binds 3' UTR of PAX9 mRNA and modulates its function leading to BMP4 downregulation and MMP9 upregulation at the transcript level. Furthermore, we surmised that miR-450b activates the Wnt signaling pathway based on gene ontology and enrichment analyses. We concluded that miR-450b has the potential as a diagnostic biomarker and could be a target candidate for COM treatment.
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Affiliation(s)
- MD Nazmul Hasan
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24, Korimoto, Kagoshima, 890-0065, Japan
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24, Korimoto, Kagoshima, 890-0065, Japan
| | - Md. Mahfuzur Rahman
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Al Asmaul Husna
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24, Korimoto, Kagoshima, 890-0065, Japan
| | - Mohammad Arif
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24, Korimoto, Kagoshima, 890-0065, Japan
| | - Indre Jasineviciute
- Department of Anatomy and Physiology, Veterinary Faculty, Lithuanian University of Health Sciences, LT-47181, Kaunas, Lithuania
| | - Daiki Kato
- Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
| | - Takayuki Nakagawa
- Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
| | - Naoki Miura
- Joint Graduate School of Veterinary Medicine, Kagoshima University, 1-21-24, Korimoto, Kagoshima, 890-0065, Japan
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24, Korimoto, Kagoshima, 890-0065, Japan
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Su Z, Wang Y, Cao J, Ma J, Wang G, Ren H, Zhang Y, Sheng K, Zhu X, Wang Y. Identification and validation of non-coding RNA-mediated high expression of IQGAP3 in poor prognosis of lung adenocarcinoma. J Gene Med 2024; 26:e3664. [PMID: 38282143 DOI: 10.1002/jgm.3664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 12/23/2023] [Accepted: 12/26/2023] [Indexed: 01/30/2024] Open
Abstract
BACKGROUND The primary reason for tumor-related deaths worldwide is lung adenocarcinoma (LUAD). The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is crucial for contributing to tumor initiation and progression. However, the precise function and molecular mechanism of IQGAP3 in LUAD remain unknown. The present study aimed to investigate the expression, prognosis, mechanism and tumor immunity associated with IQGAP3 in LUAD. METHODS The relationship between IQGAP3 and the poor prognosis of LUAD was analyzed using The Cancer Genome Atlas (TCGA) database. This analysis was further validated on lung cancer tissues and cell lines. The function of IQGAP3 was investigated by silencing it in LUAD cell lines. To predict microRNA (miRNA) and long non-coding RNA associated with IQGAP3, the starBase database was utilized, and the predictions were verified by enhancing the function of miRNA. Finally, the relationship between IQGAP3 and tumor immunity was evaluated using Spearman's correlation analysis. RESULTS TCGA database revealed that higher levels of IQGAP3 were associated with advanced tumor stage, N stage and poor prognosis in LUAD patients. To confirm that, we conducted experiments on lung cancer tissues and cell lines and found that silencing IQGAP3 significantly inhibited tumor cell proliferation and migration. The expression of IQGAP3 showed a negative correlation with has-miR-101-3p and has-miR-135a-5p, whereas it showed a positive correlation with GSEC, AC005034.3 and TYMSOS. Furthermore, the introduction of miRNA-mimics into lung cancer cell resulted in a significant inhibition of cancer cell growth and migration. Following that, the level of IQGAP3 showed a positive correlation with the infiltration of immune cells in tumors. CONCLUSIONS These results reveal that IQGAP3 significantly promotes LUAD progression and could serve as a prognostic biomarker for LUAD. Furthermore, IQGAP3 is most likely regulated by the GSEC/TYMSOS-hsa-miR-101-3p axis and the AC005034.3-hsa-miR-135a-5p axis in LUAD.
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Affiliation(s)
- Ziwei Su
- School of Life Sciences, Anhui University, Hefei, Anhui, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China
| | - Yang Wang
- School of Life Sciences, Anhui University, Hefei, Anhui, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China
| | - Jialing Cao
- School of Life Sciences, Anhui University, Hefei, Anhui, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China
| | - Jie Ma
- Department of Thoracic Surgery, Anhui Chest Hospital, Hefei, Anhui, China
| | - Guangzhao Wang
- School of Life Sciences, Anhui University, Hefei, Anhui, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China
| | - Huijuan Ren
- School of Life Sciences, Anhui University, Hefei, Anhui, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China
| | - Yihan Zhang
- School of Life Sciences, Anhui University, Hefei, Anhui, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China
| | - Kangliang Sheng
- School of Life Sciences, Anhui University, Hefei, Anhui, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China
| | - Xueying Zhu
- Department of Thoracic Surgery, Anhui Chest Hospital, Hefei, Anhui, China
| | - Yongzhong Wang
- School of Life Sciences, Anhui University, Hefei, Anhui, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, Anhui, China
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5
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Sadeghi MS, Lotfi M, Soltani N, Farmani E, Fernandez JHO, Akhlaghitehrani S, Mohammed SH, Yasamineh S, Kalajahi HG, Gholizadeh O. Recent advances on high-efficiency of microRNAs in different types of lung cancer: a comprehensive review. Cancer Cell Int 2023; 23:284. [PMID: 37986065 PMCID: PMC10661689 DOI: 10.1186/s12935-023-03133-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 11/09/2023] [Indexed: 11/22/2023] Open
Abstract
Carcinoma of the lung is among the most common types of cancer globally. Concerning its histology, it is categorized as a non-small cell carcinoma (NSCLC) and a small cell cancer (SCLC) subtype. MicroRNAs (miRNAs) are a member of non-coding RNA whose nucleotides range from 19 to 25. They are known to be critical regulators of cancer via epigenetic control of oncogenes expression and by regulating tumor suppressor genes. miRNAs have an essential function in a tumorous microenvironment via modulating cancer cell growth, metastasis, angiogenesis, metabolism, and apoptosis. Moreover, a wide range of information produced via several investigations indicates their tumor-suppressing, oncogenic, diagnostic assessment, and predictive marker functions in different types of lung malignancy. miRNA mimics or anti-miRNAs can be transferred into a lung cancer cell, with possible curative implications. As a result, miRNAs hold promise as targets for lung cancer treatment and detection. In this study, we investigate the different functions of various miRNAs in different types of lung malignancy, which have been achieved in recent years that show the lung cancer-associated regulation of miRNAs expression, concerning their function in lung cancer beginning, development, and resistance to chemotherapy, also the probability to utilize miRNAs as predictive biomarkers for therapy reaction.
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Affiliation(s)
- Mohammad Saleh Sadeghi
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohadeseh Lotfi
- School of Medicine, Tehran University of Medical Science, Tehran, Iran
| | - Narges Soltani
- School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
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Charkiewicz R, Sulewska A, Mroz R, Charkiewicz A, Naumnik W, Kraska M, Gyenesei A, Galik B, Junttila S, Miskiewicz B, Stec R, Karabowicz P, Zawada M, Miltyk W, Niklinski J. Serum Insights: Leveraging the Power of miRNA Profiling as an Early Diagnostic Tool for Non-Small Cell Lung Cancer. Cancers (Basel) 2023; 15:4910. [PMID: 37894277 PMCID: PMC10605272 DOI: 10.3390/cancers15204910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 10/05/2023] [Accepted: 10/08/2023] [Indexed: 10/29/2023] Open
Abstract
Non-small cell lung cancer is the predominant form of lung cancer and is associated with a poor prognosis. MiRNAs implicated in cancer initiation and progression can be easily detected in liquid biopsy samples and have the potential to serve as non-invasive biomarkers. In this study, we employed next-generation sequencing to globally profile miRNAs in serum samples from 71 early-stage NSCLC patients and 47 non-cancerous pulmonary condition patients. Preliminary analysis of differentially expressed miRNAs revealed 28 upregulated miRNAs in NSCLC compared to the control group. Functional enrichment analyses unveiled their involvement in NSCLC signaling pathways. Subsequently, we developed a gradient-boosting decision tree classifier based on 2588 miRNAs, which demonstrated high accuracy (0.837), sensitivity (0.806), and specificity (0.859) in effectively distinguishing NSCLC from non-cancerous individuals. Shapley Additive exPlanations analysis improved the model metrics by identifying the top 15 miRNAs with the strongest discriminatory value, yielding an AUC of 0.96 ± 0.04, accuracy of 0.896, sensitivity of 0.884, and specificity of 0.903. Our study establishes the potential utility of a non-invasive serum miRNA signature as a supportive tool for early detection of NSCLC while also shedding light on dysregulated miRNAs in NSCLC biology. For enhanced credibility and understanding, further validation in an independent cohort of patients is warranted.
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Affiliation(s)
- Radoslaw Charkiewicz
- Center of Experimental Medicine, Medical University of Bialystok, 15-369 Bialystok, Poland
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland; (A.S.); (M.K.)
| | - Anetta Sulewska
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland; (A.S.); (M.K.)
| | - Robert Mroz
- 2nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, 15-540 Bialystok, Poland;
| | - Alicja Charkiewicz
- Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, 15-089 Bialystok, Poland; (A.C.); (W.M.)
| | - Wojciech Naumnik
- 1st Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, 15-540 Bialystok, Poland;
| | - Marcin Kraska
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland; (A.S.); (M.K.)
- Department of Medical Pathomorphology, Medical University of Bialystok, 15-269 Bialystok, Poland
| | - Attila Gyenesei
- Szentagothai Research Center, Genomic and Bioinformatic Core Facility, H-7624 Pecs, Hungary; (A.G.); (B.G.)
| | - Bence Galik
- Szentagothai Research Center, Genomic and Bioinformatic Core Facility, H-7624 Pecs, Hungary; (A.G.); (B.G.)
| | - Sini Junttila
- Turku Bioscience Centre, University of Turku & Åbo Akademi University, FI-20520 Turku, Finland;
| | - Borys Miskiewicz
- Department of Thoracic Surgery, Medical University of Bialystok, 15-276 Bialystok, Poland;
| | - Rafal Stec
- Department of Oncology, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Piotr Karabowicz
- Biobank, Medical University of Bialystok, 15-269 Bialystok, Poland;
| | - Magdalena Zawada
- Department of Hematology Diagnostics and Genetics, The University Hospital, 30-688 Krakow, Poland;
| | - Wojciech Miltyk
- Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, 15-089 Bialystok, Poland; (A.C.); (W.M.)
| | - Jacek Niklinski
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland; (A.S.); (M.K.)
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Wang M, Sun Y, Yuan D, Yue S, Yang Z. Follicular fluid derived exosomal miR-4449 regulates cell proliferation and oxidative stress by targeting KEAP1 in human granulosa cell lines KGN and COV434. Exp Cell Res 2023; 430:113735. [PMID: 37517590 DOI: 10.1016/j.yexcr.2023.113735] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/11/2023] [Accepted: 07/26/2023] [Indexed: 08/01/2023]
Abstract
Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovary morphology, affecting more and more women of reproductive age. Our study aimed to explore the molecular mechanism and effect of exosomal miR-4449 on granulosa cells (GCs). Two immortalized human ovarian granulosa cells (KGN and COV434 cells) were used for in vitro functional studies. Our study found that follicular fluid (FF) derived exosomal miR-4449 was significantly decreased in women with PCOS compared with the control patients. And exosomal miR-4449 could alleviate GCs oxidative stress (OS) and promote GCs proliferation, while the opposite trend was observed after inhibiting the expression of miR-4449. In addition, we demonstrated that Kelch-like ECH-associated protein 1(KEAP1) was a direct target of miR-4449 through dual-luciferase reporter assay, and the expression patterns of KEAP1 and miR-4449 in PCOS FF-derived exosomes were exactly opposite. In addition, KEAP1/NRF2 signaling pathway may play an important role in GCs proliferation and OS. Our results demonstrated that the decreased FF-derived exosomal miR-4449 expression in PCOS might aggravate the OS of GCs and inhibit GCs proliferation via KEAP1/NRF2 signaling pathway. Exosomal miR-4449 might be a potential biomarker for the diagnosis of PCOS. Our study contributes to a new understanding of the pathogenesis of PCOS.
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Affiliation(s)
- Min Wang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Yixuan Sun
- Department of Gynecology and Obstetrics, Women and Children's Hospital of Chongqing Medical University, Chongqing, 401147, China
| | - Dong Yuan
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Song Yue
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Zhu Yang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
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Dysregulation of Serum MicroRNA after Intracerebral Hemorrhage in Aged Mice. Biomedicines 2023; 11:biomedicines11030822. [PMID: 36979801 PMCID: PMC10044892 DOI: 10.3390/biomedicines11030822] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 02/01/2023] [Accepted: 02/06/2023] [Indexed: 03/12/2023] Open
Abstract
Stroke is one of the most common diseases that leads to brain injury and mortality in patients, and intracerebral hemorrhage (ICH) is the most devastating subtype of stroke. Though the prevalence of ICH increases with aging, the effect of aging on the pathophysiology of ICH remains largely understudied. Moreover, there is no effective treatment for ICH. Recent studies have demonstrated the potential of circulating microRNAs as non-invasive diagnostic and prognostic biomarkers in various pathological conditions. While many studies have identified microRNAs that play roles in the pathophysiology of brain injury, few demonstrated their functions and roles after ICH. Given this significant knowledge gap, the present study aims to identify microRNAs that could serve as potential biomarkers of ICH in the elderly. To this end, sham or ICH was induced in aged C57BL/6 mice (18–24 months), and 24 h post-ICH, serum microRNAs were isolated, and expressions were analyzed. We identified 28 significantly dysregulated microRNAs between ICH and sham groups, suggesting their potential to serve as blood biomarkers of acute ICH. Among those microRNAs, based on the current literature, miR-124-3p, miR-137-5p, miR-138-5p, miR-219a-2-3p, miR-135a-5p, miR-541-5p, and miR-770-3p may serve as the most promising blood biomarker candidates of ICH, warranting further investigation.
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9
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Tian Y, Cui X, Guan X, Meng X, Zheng M, Wang X, Cheng G, Xia Y, Ye M. Differential expression profile of microRNAs in the lung tissues of coal workers with pneumoconiosis and patients with silicosis. Toxicol Ind Health 2023; 39:204-217. [PMID: 36840710 DOI: 10.1177/07482337231156281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2023]
Abstract
The purpose of this study was to characterize the microRNA (miRNA) profile of the lung tissues from coal workers' pneumoconiosis (CWP) and silicosis and to analyze the changes in downstream genes, biological processes, and signaling pathways based on the differently expressed miRNAs. Lung tissues from three CWP patients, eight silicosis patients, and four healthy controls were collected and analyzed for their miRNA profiles using Affymetrix® GeneChip® miRNA Arrays. Differentially expressed miRNAs (DEMs) were identified between the different groups. The miRanda and TargetScan databases were used to predict the putative target genes, and volcano and heat maps were drawn. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were then performed to screen the DEMs-associated biological process and signaling pathways, respectively. Further identification with a comprehensive literature research involving particle exposure, fibrosis, inflammation and lung cancer were used to further screen DEMs of CWP and silicosis. Microarray data showed that 375 and 88 miRNAs were differentially expressed in CWP and silicosis lung tissues compared with healthy lung tissues, while 34 miRNAs were differentially expressed in CWP compared with silicosis lung tissues. The GO and KEGG pathway analyses showed that, the target genes were mainly enriched in the TGF-β, MAPK, p53 and other signal pathways. These results provided insight into the miRNA-related underlying mechanisms of CWP and silicosis, and they provided new clues for miRNAs as biomarkers for the diagnosis and differential diagnosis of these two diseases.
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Affiliation(s)
- Yilin Tian
- National Institute for Occupational Health and Poison Control, 12415Chinese Center for Disease Control and Prevention, Beijing, China
| | - Xiuqing Cui
- Hubei Provincial Key Laboratory for Applied Toxicology, 498598Hubei Provincial Center for Disease Control and Prevention, Hubei, China
| | - Xin Guan
- Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Xiang Meng
- National Institute for Occupational Health and Poison Control, 12415Chinese Center for Disease Control and Prevention, Beijing, China
| | - Min Zheng
- National Institute for Occupational Health and Poison Control, 12415Chinese Center for Disease Control and Prevention, Beijing, China
| | - Xin Wang
- National Institute for Occupational Health and Poison Control, 12415Chinese Center for Disease Control and Prevention, Beijing, China
| | - Guoping Cheng
- Ward II of Respiratory and Critical Care Medicine, Huangshi Second Hospital, Huangshi, China
| | - Ying Xia
- Hubei Provincial Key Laboratory for Applied Toxicology, 498598Hubei Provincial Center for Disease Control and Prevention, Hubei, China
| | - Meng Ye
- National Institute for Occupational Health and Poison Control, 12415Chinese Center for Disease Control and Prevention, Beijing, China
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Ma W, Xu L, Sun X, Qi Y, Chen S, Li D, Jin Y, Chen N, Zhu X, Luo J, Li C, Zhao K, Zheng Y, Yu D. Using a human bronchial epithelial cell-based malignant transformation model to explore the function of hsa-miR-200 family in the progress of PM 2.5-induced lung cancer development. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 319:120981. [PMID: 36587786 DOI: 10.1016/j.envpol.2022.120981] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/26/2022] [Accepted: 12/28/2022] [Indexed: 06/17/2023]
Abstract
Numerous studies have revealed that ambient long-term exposure to fine particulate matter (PM2.5) is significantly related to the development of lung cancer, but the molecular mechanisms of PM2.5 exposure-induced lung cancer remains unknown. As an important epigenetic regulator, microRNAs (miRNAs) play vital roles in responding to environment exposure and various diseases including lung cancer development. Here we constructed a PM2.5-induced malignant transformed cell model and found that miR-200 family, especially miR-200a-3p, was involved in the process of PM2.5 induced lung cancer. Further investigation of the function of miR-200 family (miR-200a-3p as a representative revealed that miR-200a-3p promoted cell migration by directly suppressing TNS3 expression. These results suggested that ambient PM2.5 exposure may increase the expression of miR-200 family and then promote the proliferation and migration of lung cancer cells. Our study provided novel model and insights into the molecular mechanism of ambient PM2.5 exposure-induced lung cancer.
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Affiliation(s)
- Wanli Ma
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Lin Xu
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Xueying Sun
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Yuan Qi
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Shen Chen
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Daochuan Li
- Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Yuan Jin
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Ningning Chen
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Xiaoxiao Zhu
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Jiao Luo
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Chuanhai Li
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Kunming Zhao
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Yuxin Zheng
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China
| | - Dianke Yu
- Department of Toxicology, School of Public Health, Qingdao University, Qingdao, China.
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11
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Yang F, Zhou YL. Identification of a four-miRNA signature predicts the prognosis of papillary thyroid cancer. World J Clin Cases 2023; 11:92-103. [PMID: 36687184 PMCID: PMC9846980 DOI: 10.12998/wjcc.v11.i1.92] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/10/2022] [Accepted: 12/21/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND In recently diagnosed patients with thyroid cancer, papillary thyroid cancer (PTC), as the most common histological subtype, accounts for 90% of all cases. Although PTC is known as a relatively adolescent malignant disease, there still is a high possibility of recurrence in PTC patients with a poor prognosis. Therefore, new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) have broad application prospects as diagnostic biomarkers in cancer.
AIM To explore novel markers consisting of miRNA-associated signatures for PTC prognostication.
METHODS We obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas. The patients were randomly assigned to either a training or testing cohort.
RESULTS We discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues, which contained 172 up-regulated and 65 down-regulated miRNAs. The evaluation of differently expressed miRNAs was conducted using our risk score model. We then successfully generated a four-miRNA potential prognostic signature [risk score = (-0.001 × hsa-miR-181a-2-3p) + (0.003 × hsa-miR-138-5p) + (-0.018 × hsa-miR-424-3p) + (0.284 × hsa-miR-612)], which reliably distinguished patients from high and low risk with a significant difference in the overall survival (P < 0.01) and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts, respectively. Additionally, there was a trend indicated that high-risk patients had shorter relapse-free survival, although statistical significance was not reached (P = 0.082) in our sequencing cohort.
CONCLUSION Our results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC. Accordingly, we would recommend more radical therapy and closer follow-ups for high-risk groups.
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Affiliation(s)
- Fan Yang
- Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Yi-Li Zhou
- Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
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12
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Nguyen TTP, Suman KH, Nguyen TB, Nguyen HT, Do DN. The Role of miR-29s in Human Cancers—An Update. Biomedicines 2022; 10:biomedicines10092121. [PMID: 36140219 PMCID: PMC9495592 DOI: 10.3390/biomedicines10092121] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 08/22/2022] [Accepted: 08/24/2022] [Indexed: 11/25/2022] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that directly bind to the 3’ untranslated region (3’-UTR) of the target mRNAs to inhibit their expression. The miRNA-29s (miR-29s) are suggested to be either tumor suppressors or oncogenic miRNAs that are strongly dysregulated in various types of cancer. Their dysregulation alters the expression of their target genes, thereby exerting influence on different cellular pathways including cell proliferation, apoptosis, migration, and invasion, thereby contributing to carcinogenesis. In the present review, we aimed to provide an overview of the current knowledge on the miR-29s biological network and its functions in cancer, as well as its current and potential applications as a diagnostic and prognostic biomarker and/or a therapeutic target in major types of human cancer.
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Affiliation(s)
- Thuy T. P. Nguyen
- Division of Radiation and Genome Stability, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
| | - Kamrul Hassan Suman
- Department of Fisheries, Ministry of Fisheries and Livestock, Dhaka 1205, Bangladesh
| | - Thong Ba Nguyen
- Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA
| | - Ha Thi Nguyen
- Institute of Research and Development, Duy Tan University, Danang 550000, Vietnam
- Center for Molecular Biology, College of Medicine and Pharmacy, Duy Tan University, Danang 550000, Vietnam
- Correspondence: (H.T.N.); (D.N.D.)
| | - Duy Ngoc Do
- Department of Animal Science and Aquaculture, Dalhousie University, Truro, NS B2N 5E3, Canada
- Correspondence: (H.T.N.); (D.N.D.)
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13
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Al-Mustanjid M, Mahmud SMH, Akter F, Rahman MS, Hossen MS, Rahman MH, Moni MA. Systems biology models to identify the influence of SARS-CoV-2 infections to the progression of human autoimmune diseases. INFORMATICS IN MEDICINE UNLOCKED 2022; 32:101003. [PMID: 35818398 PMCID: PMC9259025 DOI: 10.1016/j.imu.2022.101003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 06/25/2022] [Accepted: 06/25/2022] [Indexed: 11/20/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been circulating since 2019, and its global dominance is rising. Evidences suggest the respiratory illness SARS-CoV-2 has a sensitive affect on causing organ damage and other complications to the patients with autoimmune diseases (AD), posing a significant risk factor. The genetic interrelationships and molecular appearances between SARS-CoV-2 and AD are yet unknown. We carried out the transcriptomic analytical framework to delve into the SARS-CoV-2 impacts on AD progression. We analyzed both gene expression microarray and RNA-Seq datasets from SARS-CoV-2 and AD affected tissues. With neighborhood-based benchmarks and multilevel network topology, we obtained dysfunctional signaling and ontological pathways, gene disease (diseasesome) association network and protein-protein interaction network (PPIN), uncovered essential shared infection recurrence connectivities with biological insights underlying between SARS-CoV-2 and AD. We found a total of 77, 21, 9, 54 common DEGs for SARS-CoV-2 and inflammatory bowel disorder (IBD), SARS-CoV-2 and rheumatoid arthritis (RA), SARS-CoV-2 and systemic lupus erythematosus (SLE) and SARS-CoV-2 and type 1 diabetes (T1D). The enclosure of these common DEGs with bimolecular networks revealed 10 hub proteins (FYN, VEGFA, CTNNB1, KDR, STAT1, B2M, CD3G, ITGAV, TGFB3). Drugs such as amlodipine besylate, vorinostat, methylprednisolone, and disulfiram have been identified as a common ground between SARS-CoV-2 and AD from drug repurposing investigation which will stimulate the optimal selection of medications in the battle against this ongoing pandemic triggered by COVID-19.
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Affiliation(s)
- Md Al-Mustanjid
- Department of Software Engineering, Faculty of Science and Information Technology, Daffodil International University, Dhaka-1207, Bangladesh
| | - S M Hasan Mahmud
- Department of Computer Science, American International University-Bangladesh, Dhaka, 1229, Bangladesh
| | - Farzana Akter
- Department of Software Engineering, Faculty of Science and Information Technology, Daffodil International University, Dhaka-1207, Bangladesh
| | - Md Shazzadur Rahman
- Department of Computer Science & Engineering, Faculty of Science and Information Technology, Daffodil International University, Dhaka-1207, Bangladesh
| | - Md Sajid Hossen
- Department of Software Engineering, Faculty of Science and Information Technology, Daffodil International University, Dhaka-1207, Bangladesh
| | - Md Habibur Rahman
- Department of Computer Science and Engineering, Islamic University, Kushtia-7003, Bangladesh
| | - Mohammad Ali Moni
- Department of Computer Science and Engineering, Pabna Science & Technology University, Pabna, 6600, Bangladesh
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14
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Khan MM, Serajuddin M, Malik MZ. Identification of microRNA and gene interactions through bioinformatic integrative analysis for revealing candidate signatures in prostate cancer. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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15
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Gong X, Liu Y, Zheng C, Tian P, Peng M, Pan Y, Li X. Establishment of a 4-miRNA Prognostic Model for Risk Stratification of Patients With Pancreatic Adenocarcinoma. Front Oncol 2022; 12:827259. [PMID: 35186758 PMCID: PMC8851918 DOI: 10.3389/fonc.2022.827259] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 01/17/2022] [Indexed: 12/12/2022] Open
Abstract
Pancreatic adenocarcinomas (PAADs) often remain undiagnosed until later stages, limiting treatment options and leading to poor survival. The lack of robust biomarkers complicates PAAD prognosis, and patient risk stratification remains a major challenge. To address this issue, we established a panel constructed by four miRNAs (miR-4444-2, miR-934, miR-1301 and miR-3655) based on The Cancer Genome Atlas (TCGA) and Human Cancer Metastasis Database (HCMDB) to predicted the prognosis of PAAD patients. Then, a risk prediction model of these four miRNAs was constructed by using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) regression analysis. This model stratified TCGA PAAD cohort into the low-risk and high-risk groups based on the panel-based risk score, which was significantly associated with 1-, 2-, 3-year OS (AUC=0.836, AUC=0.844, AUC=0.952, respectively). The nomogram was then established with a robust performance signature for predicting prognosis compared to clinical characteristics of pancreatic cancer (PC) patients, including age, gender and clinical stage. Moreover, two GSE data were validated the expressions of 4 miRNAs with prognosis/survival outcome in PC. In the external clinical sample validation, the high-risk group with the upregulated expressions of miR-934/miR-4444-2 and downregulated expressions of miR-1301/miR-3655 were indicated a poor prognosis. Furthermore, the cell counting kit-8 (CCK-8) assay, clone formation, transwell and wound healing assay also confirmed the promoting effect of miR-934/miR-4444-2 and the inhibiting effect of miR-1301/miR-3655 in PC cell proliferation and migration. Taken together, we identified a new 4-miRNA risk stratification model could be used in predicting prognosis in PAAD.
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Affiliation(s)
- Xun Gong
- Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China.,College of Electronics and Information Engineering, Shenzhen University, Shenzhen, China
| | - Yuchen Liu
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.,Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Chenglong Zheng
- Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China
| | - Peikai Tian
- Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China
| | - Minjie Peng
- Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China
| | - Yihang Pan
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.,Big Data Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xiaowu Li
- Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China
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16
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Yu J, He X, Fang C, Wu H, Hu L, Xue Y. MicroRNA‑200a‑3p and GATA6 are abnormally expressed in patients with non‑small cell lung cancer and exhibit high clinical diagnostic efficacy. Exp Ther Med 2022; 23:281. [PMID: 35317445 PMCID: PMC8908458 DOI: 10.3892/etm.2022.11210] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 11/16/2021] [Indexed: 11/15/2022] Open
Abstract
Lung cancer is one of the main threats to human health. Survival of patients with lung cancer depends on timely detection and diagnosis. Among the genetic irregularities that control cancer development and progression, there are microRNAs (miRNAs/miRs). The present study aimed to investigate the expression patterns of miR-200a-3p and transcription factor GATA-6 (GATA6) in peripheral blood of patients with non-small cell lung cancer (NSCLC) and their clinical significance. The expression patterns of miR-200a-3p and GATA6 in the peripheral blood of patients with NSCLC and healthy subjects were measured via reverse transcription-quantitative PCR. The correlation between GATA6/miR-200a-3p expression and their diagnostic efficacy were analyzed by receiver operating characteristic curve analysis. The association between miR-200a-3p/GATA6 expression with the patient clinicopathological characteristics, and their correlation with carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCCAg) were evaluated. The cumulative survival rate was examined, and whether miR-200a-3p and GATA6 expression levels were independently correlated with the prognosis of NSCLC was analyzed using multivariate logistic regression model. The results demonstrated that the expression of miR-200a-3p was high and that of GATA6 was low in the peripheral blood of patients with NSCLC, and both exhibited high clinical diagnostic efficacy. miR-200a-3p was revealed to target GATA6 by dual-luciferase assay. miR-200a-3p in the peripheral blood was correlated with TNM stage, lymph node metastasis and distal metastasis, while GATA6 in the peripheral blood was correlated with TNM stage and lymph node metastasis. miR-200a-3p and GATA6 were positively correlated with CEA and SCCAg, but not with NSE. High expression of miR-200a-3p and low expression of GATA6 predicted poor prognosis in patients with NSCLC. After adjusting for TNM stage, lymph node metastasis, distance metastasis, GATA6, CEA, NSE and SCCAg in the logistic regression model, it was indicated that the high expression of miR-200a-3p increased the risk of death in patients with NSCLC. Collectively, it was revealed that miR-200a-3p and GATA6 were abnormally expressed in the peripheral blood of patients with NSCLC. Serum levels of miR-200a-3p >1.475 and GATA6 <1.195 may assist the early diagnosis of NSCLC. GATA6 may function in NSCLC as a miR-200a-3p target, which may provide a future reference for NSCLC early diagnosis and treatment.
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Affiliation(s)
- Jie Yu
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| | - Xinyun He
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| | - Chunju Fang
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| | - Haixia Wu
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
| | - Lei Hu
- Department of Laboratory Medicine, Guizhou Women's and Children's Hospital, Guiyang, Guizhou 550003, P.R. China
| | - Yingbo Xue
- Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550001, P.R. China
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17
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LncRNA HOTTIP Knockdown Attenuates Acute Myocardial Infarction via Regulating miR-92a-2/c-Met Axis. Cardiovasc Toxicol 2022; 22:352-364. [PMID: 35044621 PMCID: PMC8907089 DOI: 10.1007/s12012-021-09717-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 12/21/2021] [Indexed: 12/11/2022]
Abstract
Increasing investigations have focused on long non-coding RNAs (lncRNAs) in various human diseases, including acute myocardial infarction (AMI). Although lncRNA HOTTIP has been identified to play an important role in coronary artery diseases, its role and specific mechanism in AMI remain unclear. To investigate the potential role of HOTTIP in MI, HOTTIP expression in hypoxia-treated cardiomyocytes and myocardial tissues of MI mice was evaluated. The potential targets of HOTTIP and miR-92a-2 were predicted using Starbase and Targetscan. To further determine the cardio-protective effects of HOTTIP in vivo, si-HOTTIP and miR-92a-2 mimics were individually or co-injected into mice through intramyocardial injection. Moreover, their roles were further confirmed in rescue experiments. HOTTIP was significantly upregulated in ischemic myocardium of MI mice and hypoxia-induced cardiomyocytes. Moreover, HOTTIP knockdown markedly promoted cardiomyocyte growth and inhibited cardiomyocyte apoptosis in vitro. Luciferase reporter assay showed that HOTTIP could directly sponge miR-92a-2 to negatively regulate miR-92a-2 expression. In addition, c-Met was identified as a direct target of miR-92a-2, and their correlation was confirmed by luciferase reporter assay. MiR-92a-2 overexpression significantly enhanced the protective effect of HOTTIP knockdown against AMI through partially inhibiting c-Met expression. Our results demonstrated that HOTTIP downregulation attenuated AMI progression via the targeting miR-92a-2/c-Met axis and suggested that HOTTIP might be a potential therapeutic target for AMI.
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18
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Wu L, Yang N, Liu Q, Bai Y, Gao B. MiR-200c-3p affects cochlear hair cells damaged by oxidative stress via modulating Taok1 expression. Am J Transl Res 2021; 13:13665-13673. [PMID: 35035705 PMCID: PMC8748156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 10/26/2021] [Indexed: 06/14/2023]
Abstract
OBJECTIVE The aim of this study was to elucidate the role of miR-200c-3p in cochlear hair cells injured by oxidative stress (OS) and the underlying mechanisms. METHODS The OS injury model of HEI-OC1 cells was induced by 100 μmol/L tert-butyl hydroperoxide (t-BHP). The expression of miR-200c-3p in HEI-OC1 was detected by RT-PCR, the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), Catalase (CAT), and malondialdehyde (MDA) were determined with ELISA, and the expression levels of Taok1 and apoptosis-related proteins were measured by Western Blot. Flow cytometry was used to detect cell apoptosis. RESULTS Real-time polymerase chain reaction (RT-qPCR) analysis identified down-regulated miR-200c-3p and up-regulated Taok1 in HEI-OC1 cells damaged by OS, as well as an inverse association between miR-200c-3p and Taok1. Cell tests confirmed that miR-200c-3p overexpression could effectively inhibit the OS response and apoptosis of HEI-OC1 cells. Bioinformatics prediction and dual luciferase reporter assay revealed that Taok1 was a direct target of miR-200c-3p. Taok1 overexpression could reverse the protective action of miR-200c-3p overexpression on the OS injury of HEI-OC1 cells. CONCLUSIONS Given the capacity of miR-200c-3p to suppress the OS and apoptosis of HEI-OC1 cells via targeting Taok1, it can be a novel and potential therapeutic target for cochlear hair cell injury.
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Affiliation(s)
- Lihua Wu
- Department of Otolaryngology, Head and Neck Surgery, Fujian Medical University ShengLi Clinical College, Fujian Provincial HospitalFuzhou 350001, Fujian, China
- Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General HospitalBeijing 100036, China
- Department of Otolaryngology, Head and Neck Surgery, Nanfang Hospital, Southern Medical UiversityGuangzhou 510515, Guangdong, China
| | - Ning Yang
- Department of Otolaryngology, Head and Neck Surgery, First Affiliated Hospital of China Medical UniversityShenyang 110001, Liaoning, China
| | - Qinghua Liu
- Department of Otolaryngology, Head and Neck Surgery, Fujian Medical University ShengLi Clinical College, Fujian Provincial HospitalFuzhou 350001, Fujian, China
| | - Yue Bai
- Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005, Fujian, China
| | - Bo Gao
- Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General HospitalBeijing 100036, China
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19
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Lou X, Wang D, Gu Z, Li T, Ren L. Mechanism of microRNA regulating the progress of atherosclerosis in apoE-deficient mice. Bioengineered 2021; 12:10994-11006. [PMID: 34775883 PMCID: PMC8809940 DOI: 10.1080/21655979.2021.2004979] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/05/2021] [Accepted: 11/05/2021] [Indexed: 12/24/2022] Open
Abstract
MicroRNAs play important roles in atherosclerogenesis and are important novel pharmaceutic targets in atherosclerosis management. The whole spectrum of miRNAs dysregulation is still under intense investigation. This study intends to identify more novel dysregulated microRNAs in atherosclerotic mice. Half of eight-week-old male ApoE-/- mice were fed with high-fat-diet for 12 weeks as a model mice, and the remaining half of ApoE-/- mice were fed with a normal-diet as a control. A serum lipid profile was performed with ELISA kits, and atherosclerotic lesions were assessed. Aortic tissues were dissected for gene expression profiling using a Multispecies miRNA 4.0 Array, and significant differentially expressed miRNAs were identified with fold change ≥ 2 and p < 0.05. Real-time quantitative PCR was used to validate microarray gene expression data on selected genes. Predicted target genes were extracted and subjected to bioinformatic analysis for molecular function and pathway enrichment analysis. Model mice showed a 15.32% atherosclerotic lesion compared to 1.52% in the control group. A total of 25 significant differentially expressed microRNAs were identified, with most of them (24/25) downregulated. Real-time quantitative PCR confirmed the GeneChip data. Bioinformatic analysis of predicted target genes identified high involvement of the PI3K/Akt/mTOR signaling pathway. Microarray profiling of miRNAs in high-fat-fed Model mice identified 25 differentially expressed miRNAs, including some novel miRNAs, and the PI3K/Akt/mTOR signaling pathway is highly enriched in the predicted target genes. The novel identified dysregulated miRNAs suggest a broader spectrum of miRNA dysregulation in the progression of atherosclerosis and provide more research and therapeutic targets for atherosclerosis.
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Affiliation(s)
- Xiaoqian Lou
- Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, Jilin, China
- Department of Endocrinology, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Dawei Wang
- Department of Emergency, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China
| | - Zehui Gu
- Department of Pathology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, People's Republic of China
| | - Tengteng Li
- Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, Jilin, China
| | - Liqun Ren
- Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, Jilin, China
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20
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Hassanein SS, Ibrahim SA, Abdel-Mawgood AL. Cell Behavior of Non-Small Cell Lung Cancer Is at EGFR and MicroRNAs Hands. Int J Mol Sci 2021; 22:12496. [PMID: 34830377 PMCID: PMC8621388 DOI: 10.3390/ijms222212496] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 11/13/2021] [Accepted: 11/17/2021] [Indexed: 12/18/2022] Open
Abstract
Lung cancer is a complex disease associated with gene mutations, particularly mutations of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) and epidermal growth factor receptor (EGFR). Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the two major types of lung cancer. The former includes most lung cancers (85%) and are commonly associated with EGFR mutations. Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, and osimertinib, are effective therapeutic agents in EGFR-mutated NSCLC. However, their effectiveness is limited by the development (acquired) or presence of intrinsic drug resistance. MicroRNAs (miRNAs) are key gene regulators that play a profound role in the development and outcomes for NSCLC via their role as oncogenes or oncosuppressors. The regulatory role of miRNA-dependent EGFR crosstalk depends on EGFR signaling pathway, including Rat Sarcoma/Rapidly Accelerated Fibrosarcoma/Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase 1/2 (Ras/Raf/MEK/ERK1/2), Signal Transducer and Activator of Transcription (STAT), Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-kB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Janus kinase 1 (JAK1), and growth factor receptor-bound protein 2 (GRB2). Dysregulated expression of miRNAs affects sensitivity to treatment with EGFR-TKIs. Thus, abnormalities in miRNA-dependent EGFR crosstalk can be used as diagnostic and prognostic markers, as well as therapeutic targets in NSCLC. In this review, we present an overview of miRNA-dependent EGFR expression regulation, which modulates the behavior and progression of NSCLC.
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Affiliation(s)
- Sarah Sayed Hassanein
- Biotechnology Program, Basic and Applied Sciences (BAS) Institute, Egypt-Japan University of Science and Technology (E-JUST), Alexandria 21934, Egypt;
- Department of Zoology, Faculty of Science, Cairo University, Giza 12613, Egypt;
| | | | - Ahmed Lotfy Abdel-Mawgood
- Biotechnology Program, Basic and Applied Sciences (BAS) Institute, Egypt-Japan University of Science and Technology (E-JUST), Alexandria 21934, Egypt;
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21
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Guo H, Lin S, Gan Z, Xie J, Zhou J, Hu M. lncRNA FOXD3-AS1 promotes the progression of non-small cell lung cancer by regulating the miR-135a-5p/CDK6 axis. Oncol Lett 2021; 22:853. [PMID: 34733371 PMCID: PMC8561623 DOI: 10.3892/ol.2021.13114] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 06/22/2021] [Indexed: 12/22/2022] Open
Abstract
Long non-coding RNA (lncRNA) is essential to the development and progression of malignant human cancer. Growing evidence suggests that the lncRNA forkhead box D3 antisense 1 (FOXD3-AS1) is a crucial regulatory effector for multiple cancer types and is closely associated with poor prognosis. However, in most cases, the molecular mechanism underlying the role of FOXD3-AS1 in cancer development has not yet been fully elucidated. The present study focused on non-small cell lung cancer (NSCLC) in order to gain insight into how FOXD3-AS1 drives cancer progression. First, FOXD3-AS1 expression in NSCLC tissue samples was detected using reverse transcription-quantitative (RT-qPCR). Moreover, cell proliferation and apoptosis were determined using Cell Counting Kit-8 assays and flow cytometry, respectively. A luciferase reporter assay was then performed to determine whether there was a direct binding association between FOXD3-AS1 and microRNA (miR)-135a-5p. Lastly, a tumor subcutaneous xenograft model was established to examine the role of FOXD3-AS1 in tumor growth. FOXD3-AS1 was significantly overexpressed in NSCLC tissue samples and cell lines compared with normal tissue samples and cells. FOXD3-AS1 silencing expression significantly inhibited A549 and H1229 cell proliferation while inducing apoptosis compared with sh-NC group. The luciferase reporter assay demonstrated the direct binding interaction between FOXD3-AS1 and miR-135a-5p. Moreover, FOXD3-AS1 silencing led to the upregulation of miR-135a-5p in A549 and H1229 cells compared with sh-NC group. It was also demonstrated that miR-135a-5p could bind to the 3′ untranslated region of cyclin-dependent kinase 6 (CDK6) and negatively modulate its transcription. miR-135a-5p knockdown or CDK6 overexpression reversed the inhibition on cell proliferation and apoptosis following FOXD3-AS1 knockdown. Altogether, the present study suggests that FOXD3-AS1 sponges miR-135a-5p to promote cell proliferation and concomitantly inhibit apoptosis by regulating CDK6 expression in NSCLC cells.
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Affiliation(s)
- Haiyan Guo
- Department of Respiratory Medicine, People's Hospital of Nanhai District (Affiliated Nanhai Hospital of Southern Medical University), Foshan, Guangdong 528200, P.R. China.,Department of Respiratory Medicine, The Sixth Affiliated Hospital, South China University of Technology, Foshan, Guangdong 528200, P.R. China
| | - Shufang Lin
- Department of Respiratory Medicine, People's Hospital of Nanhai District (Affiliated Nanhai Hospital of Southern Medical University), Foshan, Guangdong 528200, P.R. China.,Department of Respiratory Medicine, The Sixth Affiliated Hospital, South China University of Technology, Foshan, Guangdong 528200, P.R. China
| | - Zhenyong Gan
- Department of Respiratory Medicine, People's Hospital of Nanhai District (Affiliated Nanhai Hospital of Southern Medical University), Foshan, Guangdong 528200, P.R. China.,Department of Respiratory Medicine, The Sixth Affiliated Hospital, South China University of Technology, Foshan, Guangdong 528200, P.R. China
| | - Jinglian Xie
- Department of Respiratory Medicine, The Sixth Affiliated Hospital, South China University of Technology, Foshan, Guangdong 528200, P.R. China.,Department of Cardiothoracic Surgery, People's Hospital of Nanhai District (Affiliated Nanhai Hospital of Southern Medical University), Foshan, Guangdong 528200, P.R. China
| | - Jiaming Zhou
- Department of Respiratory Medicine, The Fifth People's Hospital of Nanhai District, Foshan, Guangdong 528200, P.R. China
| | - Ming Hu
- Department of Urology, The Sixth Affiliated Hospital, South China University of Technology, Foshan, Guangdong 528200, P.R. China.,Department of Urology, People's Hospital of Nanhai District (Affiliated Nanhai Hospital of Southern Medical University), Foshan, Guangdong 528200, P.R. China
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22
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Wang S, Tang W, Ma L, Yang J, Huang K, Du X, Luo A, Shen W, Ding T, Ye S, Zhou S, Yang S, Wang S. MiR-145 regulates steroidogenesis in mouse primary granulosa cells through targeting Crkl. Life Sci 2021; 282:119820. [PMID: 34273377 DOI: 10.1016/j.lfs.2021.119820] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 06/28/2021] [Accepted: 07/06/2021] [Indexed: 12/13/2022]
Abstract
AIMS It has been demonstrated that miR-145 is expressed in primordial follicles and modulates the initiation of primordial follicle development. We aimed to explore the function of miR-145 in mouse granulosa cells (mGCs). MATERIALS AND METHODS The proliferation and differentiation of GCs were examined via MTT, EDU assay, QRT-PCR, ELISA and electron microscope analysis. The target of miR-145 was determined by bioinformatics analysis and luciferase reporter assay and the molecular mechanisms were examined via western blot and quantitative Real-Time RT-PCR. KEY FINDINGS We proved that down-regulation of miR-145 could inhibit GCs proliferation and differentiation. In addition, we provided evidence that Crkl was the target gene of miR-145. The miR-145 antagomir caused an increase in Crkl expression and activation of the JNK/p38 MAPK pathway. Overexpression of Crkl with pEGFP-N1-Crkl vector inhibited GCs differentiation and progesterone synthesis as well as activation of the JNK/p38 MAPK pathway. SIGNIFICANCE Our study shows that miR-145 targets Crkl and through the JNK/p38 MAPK signaling pathway promotes the GCs proliferation, differentiation, and steroidogenesis. MiR-145 may play an important role in the ovarian physiology and pathology.
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Affiliation(s)
- Shuo Wang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Weicheng Tang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Lanfang Ma
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China; Department of Obstetrics and Gynecology, Guiyang Maternity and Child Health Care Hospital, Guiyang, Guizhou, People's Republic of China
| | - Jun Yang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China; Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, People's Republic of China
| | - Kecheng Huang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Xiaofang Du
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China; Department of Obstetrics and Gynecology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Aiyue Luo
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Wei Shen
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Ting Ding
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Shuangmei Ye
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Su Zhou
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Shuhong Yang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
| | - Shixuan Wang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
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23
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Xiao K, Liu S, Xiao Y, Wang Y, Zhu Z, Wang Y, Tong D, Jiang J. Bioinformatics prediction of differential miRNAs in non-small cell lung cancer. PLoS One 2021; 16:e0254854. [PMID: 34288959 PMCID: PMC8294502 DOI: 10.1371/journal.pone.0254854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 07/03/2021] [Indexed: 12/26/2022] Open
Abstract
Background Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. The drug resistance of NSCLC has clinically increased. This study aimed to screen miRNAs associated with NSCLC using bioinformatics analysis. We hope that the screened miRNA can provide a research direction for the subsequent treatment of NSCLC. Methods We screened out the common miRNAs after compared the NSCLC-related genes in the TCGA database and GEO database. Selected miRNA was performed ROC analysis, survival analysis, and enrichment analysis (GO term and KEGG pathway). Results A total of 21 miRNAs were screened in the two databases. And they were all highly expressed in normal and low in cancerous tissues. Hsa-mir-30a was selected by ROC analysis and survival analysis. Enrichment analysis showed that the function of hsa-mir-30a is mainly related to cell cycle regulation and drug metabolism. Conclusion Our study found that hsa-mir-30a was differentially expressed in NSCLC, and it mainly affected NSCLC by regulating the cell cycle and drug metabolism.
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Affiliation(s)
- Kui Xiao
- Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- The Respiratory Disease Diagnosis and Treatment Center of Hunan Province, Changsha, Hunan, China
| | - Shenggang Liu
- Department of Pulmonary and Critical Care Medicine, University of South China Affiliated Changsha Central Hospital, Changsha City, Hunan Province, China
| | - Yijia Xiao
- Department of Pulmonary and Critical Care Medicine, University of South China Affiliated Changsha Central Hospital, Changsha City, Hunan Province, China
| | - Yang Wang
- Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Zhiruo Zhu
- Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- The Respiratory Disease Diagnosis and Treatment Center of Hunan Province, Changsha, Hunan, China
| | - Yaohui Wang
- Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- The Respiratory Disease Diagnosis and Treatment Center of Hunan Province, Changsha, Hunan, China
| | - De Tong
- Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, China
- The Respiratory Disease Diagnosis and Treatment Center of Hunan Province, Changsha, Hunan, China
| | - Jiehan Jiang
- Department of Pulmonary and Critical Care Medicine, University of South China Affiliated Changsha Central Hospital, Changsha City, Hunan Province, China
- * E-mail:
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24
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Han F, Chen G, Guo Y, Li B, Sun Y, Qi X, Tian H, Zhao X, Zhang H. MicroRNA-4491 enhances cell proliferation and inhibits cell apoptosis in non-small cell lung cancer via targeting TRIM7. Oncol Lett 2021; 22:591. [PMID: 34149902 PMCID: PMC8200940 DOI: 10.3892/ol.2021.12852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 02/09/2021] [Indexed: 11/26/2022] Open
Abstract
MicroRNAs (miRNAs) are involved in the development of non-small cell lung cancer (NSCLC). However, the biological roles of several aberrantly expressed miRNAs have not been explored yet. In the present study, miR-4491 was identified as a novel upregulated miRNA in NSCLC tissues and cell lines. Downregulation of miR-4491 by a miR-4491 inhibitor inhibited the proliferation and triggered the apoptosis of NSCLC cells. Tripartite motif containing 7 (TRIM7), a tumor suppressor gene expressed in NSCLC, was demonstrated in the present study to be directly targeted by miR-4491. This finding was verified by bioinformatics analysis, reverse transcription-quantitative PCR, western blotting and dual luciferase reporter assays. Furthermore, downregulation of miR-4491 inactivated nuclear factor-κB signaling via induction of TRIM7. In addition, TRIM7 silencing attenuated the effect of miR-4491 inhibitor in NSCLC cells. The decreased TRIM7 level in NSCLC tissues was negatively correlated with miR-4491 expression in NSCLC tissues. In conclusion, the findings from this study demonstrated that miR-4491 expression was upregulated in NSCLC tissues and cells and that miR-4491 may promote NSCLC progression via targeting TRIM7.
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Affiliation(s)
- Fei Han
- Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
| | - Gang Chen
- Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
| | - Yi Guo
- Department of Respiratory Diseases, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
| | - Bo Li
- Department of Thoracic Radiotherapy, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
| | - Yanlong Sun
- Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
| | - Xiangqian Qi
- Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
| | - Hanji Tian
- Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
| | - Xinfei Zhao
- Taiyuan Jinyu Clinical Laboratory, Taiyuan, Shanxi 030013, P.R. China
| | - Hongguang Zhang
- Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
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25
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Lei GL, Niu Y, Cheng SJ, Li YY, Bai ZF, Yu LX, Hong ZX, Liu H, Liu HH, Yan J, Gao Y, Zhang SG, Chen Z, Li RS, Yang PH. Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma. World J Gastroenterol 2021; 27:2586-2602. [PMID: 34092977 PMCID: PMC8160624 DOI: 10.3748/wjg.v27.i20.2586] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/10/2021] [Accepted: 04/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a malignancy found globally. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play critical roles in HCC. However, the function of lncRNA in HCC remains poorly understood. AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms. METHODS We measured the expression of lncRNA W42 in HCC tissues and cells (Huh7 and SMMC-7721) by quantitative reverse transcriptase polymerase chain reaction. Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression. HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42. Cell functions were detected by cell counting Kit-8 (CCK-8), colony formation, flow cytometry and Transwell assays. The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays. An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo. The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC. RESULTS In this study, we identified a novel lncRNA (lncRNA W42), and investigated its biological functions and clinical significance in HCC. LncRNA W42 expression was upregulated in HCC tissues and cells. Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC, and inhibited cell apoptosis. LncRNA W42 directly bound to DBN1 and activated the downstream pathway. LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo. The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times. CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42, which is upregulated in HCC, may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.
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Affiliation(s)
- Guang-Lin Lei
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yan Niu
- Inner Mongolia Medical University, Hohhot 010110, Inner Mongolia Autonomous Region, China
| | - Si-Jie Cheng
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yuan-Yuan Li
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhi-Fang Bai
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Ling-Xiang Yu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhi-Xian Hong
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hu Liu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hong-Hong Liu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Jin Yan
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yuan Gao
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Shao-Geng Zhang
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhu Chen
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Rui-Sheng Li
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Peng-Hui Yang
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
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Yan Z, Hong S, Song Y, Bi M. microR-4449 Promotes Colorectal Cancer Cell Proliferation via Regulation of SOCS3 and Activation of STAT3 Signaling. Cancer Manag Res 2021; 13:3029-3039. [PMID: 33854373 PMCID: PMC8039016 DOI: 10.2147/cmar.s266153] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 10/21/2020] [Indexed: 12/28/2022] Open
Abstract
Introduction Dysregulation of microRNAs (miRNAs), which represented a critical level of gene expression modulation, regulated the development of colorectal cancer. However, the functions of numerous miRNAs remain unclear in colorectal cancer. Methods The microarray data of GSE115513 were retrieved; subsequently, the differentially expressed miRNAs between 411 colon tumors and 381 normal colon mucosa were analyzed. Real-time PCR (RT-qPCR) and bioinformatic analysis were applied to examine the expression of miR-4449 in collected colorectal tumors and published microarray data. The activity of signal transducer and activator of transcription 3 (STAT3) signaling was detected by Western blotting and RT-qPCR. Dual-Luciferase assay and bioinformatic analysis were used to confirm the interaction between suppressor of cytokine signaling 3 (SOCS3) and miR-4449. Loss of function and rescue assays were performed to study the involvement of miR-4449 and SOCS3 in cell proliferation and apoptosis of colorectal cancer. Results Herein, we identified miR-4449 as a novel upregulated miRNA in colorectal cancer. Our data suggested that miR-4449 downregulation blocked the proliferation of colorectal cancer cells accompanied with the elevation of cell apoptosis. Decreased expression of miR-4449 led to inactivation of STAT3 pathway as indicated by dephosphorylation of STAT3 and downregulation of STAT3 target genes, including vascular endothelial growth factor (VEGF), c-Myc, baculovirus inhibitor of apoptosis containing 5 (BIRC5). Furthermore, SOCS3, a negative regulator of STAT3 pathway, was found to be a target gene of miR-4449. The data also showed that the inactivation of STAT3 pathway by miR-4449 inhibitor was realized by targeting SOCS3. Moreover, the biological function of miR-4449 downregulation was reversed by SOCS3 knockdown in colorectal cancer cells. Conclusion The current study revealed that miR-4449 promoted cell proliferation of colorectal cancer and was a promising potential therapeutic target for colorectal cancer.
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Affiliation(s)
- Zhenkun Yan
- Department of Endoscopy Center, The Third Hospital of Jilin University, Changchun, Jilin, 130022, People's Republic of China
| | - Sen Hong
- Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130022, People's Republic of China
| | - Yumei Song
- Department of Thoracic Oncology, Tumor Hospital of Jilin Province, Changchun, Jilin, 130022, People's Republic of China
| | - Miaomiao Bi
- Department of Ophthalmology, The Third Hospital of Jilin University, Changchun, Jilin, 130022, People's Republic of China
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Zhong S, Golpon H, Zardo P, Borlak J. miRNAs in lung cancer. A systematic review identifies predictive and prognostic miRNA candidates for precision medicine in lung cancer. Transl Res 2021; 230:164-196. [PMID: 33253979 DOI: 10.1016/j.trsl.2020.11.012] [Citation(s) in RCA: 102] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 11/05/2020] [Accepted: 11/24/2020] [Indexed: 02/08/2023]
Abstract
Lung cancer (LC) is the leading cause of cancer-related death worldwide and miRNAs play a key role in LC development. To better diagnose LC and to predict drug treatment responses we evaluated 228 articles encompassing 16,697 patients and 12,582 healthy controls. Based on the criteria of ≥3 independent studies and a sensitivity and specificity of >0.8 we found blood-borne miR-20a, miR-10b, miR-150, and miR-223 to be excellent diagnostic biomarkers for non-small cell LC whereas miR-205 is specific for squamous cell carcinoma. The systematic review also revealed 38 commonly regulated miRNAs in tumor tissue and the circulation, thus enabling the prediction of histological subtypes of LC. Moreover, theranostic biomarker candidates with proven responsiveness to checkpoint inhibitor treatments were identified, notably miR-34a, miR-93, miR-106b, miR-181a, miR-193a-3p, and miR-375. Conversely, miR-103a-3p, miR-152, miR-152-3p, miR-15b, miR-16, miR-194, miR-34b, and miR-506 influence programmed cell death-ligand 1 and programmed cell death-1 receptor expression, therefore providing a rationale for the development of molecularly targeted therapies. Furthermore, miR-21, miR-25, miR-27b, miR-19b, miR-125b, miR-146a, and miR-210 predicted response to platinum-based treatments. We also highlight controversial reports on specific miRNAs. In conclusion, we report diagnostic miRNA biomarkers for in-depth clinical evaluation. Furthermore, in an effort to avoid unnecessary toxicity we propose predictive biomarkers. The biomarker candidates support personalized treatment decisions of LC patients and await their confirmation in randomized clinical trials.
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Affiliation(s)
- Shen Zhong
- Centre for Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany
| | - Heiko Golpon
- Department of Pneumology, Hannover Medical School, Hannover, Germany
| | - Patrick Zardo
- Clinic for Cardiothoracic and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Jürgen Borlak
- Centre for Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany.
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28
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Budakoti M, Panwar AS, Molpa D, Singh RK, Büsselberg D, Mishra AP, Coutinho HDM, Nigam M. Micro-RNA: The darkhorse of cancer. Cell Signal 2021; 83:109995. [PMID: 33785398 DOI: 10.1016/j.cellsig.2021.109995] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/25/2021] [Accepted: 03/25/2021] [Indexed: 12/21/2022]
Abstract
The discovery of micro RNAs (miRNA) in cancer has opened up new vistas for researchers in recent years. Micro RNAs area set of small, endogenous, highly conserved, non-coding RNAs that control the expression of about 30% genes at post-transcriptional levels. Typically, microRNAs impede the translation and stability of messenger RNAs (mRNA), control genes associated with cellular processes namely inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and migration. Compelling findings revealed that miRNA mutations or disruption correspond to diverse human cancers and suggest that miRNAs can function as tumor suppressors or oncogenes. Here we summarize the literature on these master regulators in clinical settings from last three decades as both abrupt cancer therapeutics and as an approach to sensitize tumors to chemotherapy. This review highlights (I) the prevailing perception of miRNA genomics, biogenesis, as well as function; (II) the significant advancements in regulatory mechanisms in the expression of carcinogenic genes; and (III) explains, how miRNA is utilized as a diagnostic and prognostic biomarker for the disease stage indicating survival as well as therapeutic targets in cancer.
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Affiliation(s)
- Mridul Budakoti
- Department of Biochemistry, H. N. B. Garhwal University, Srinagar Garhwal 246174, Uttarakhand, India
| | - Abhay Shikhar Panwar
- Department of Biochemistry, H. N. B. Garhwal University, Srinagar Garhwal 246174, Uttarakhand, India
| | - Diksha Molpa
- Department of Biochemistry, H. N. B. Garhwal University, Srinagar Garhwal 246174, Uttarakhand, India
| | - Rahul Kunwar Singh
- Department of Microbiology, H. N. B. Garhwal University, Srinagar Garhwal 246174, Uttarakhand, India
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar.
| | - Abhay Prakash Mishra
- Department of Pharmaceutical Chemistry, H. N. B. Garhwal University, Srinagar Garhwal 246174, Uttarakhand, India.
| | | | - Manisha Nigam
- Department of Biochemistry, H. N. B. Garhwal University, Srinagar Garhwal 246174, Uttarakhand, India.
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Sima M, Rossnerova A, Simova Z, Rossner P. The Impact of Air Pollution Exposure on the MicroRNA Machinery and Lung Cancer Development. J Pers Med 2021; 11:60. [PMID: 33477935 PMCID: PMC7833364 DOI: 10.3390/jpm11010060] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 12/14/2022] Open
Abstract
Small non-coding RNA molecules (miRNAs) play an important role in the epigenetic regulation of gene expression. As these molecules have been repeatedly implicated in human cancers, they have been suggested as biomarkers of the disease. Additionally, miRNA levels have been shown to be affected by environmental pollutants, including airborne contaminants. In this review, we searched the current literature for miRNAs involved in lung cancer, as well as miRNAs deregulated as a result of exposure to air pollutants. We then performed a synthesis of the data and identified those molecules commonly deregulated under both conditions. We detected a total of 25 miRNAs meeting the criteria, among them, miR-222, miR-21, miR-126-3p, miR-155 and miR-425 being the most prominent. We propose these miRNAs as biomarkers of choice for the identification of human populations exposed to air pollution with a significant risk of developing lung cancer.
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Affiliation(s)
- Michal Sima
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague, Czech Republic; (M.S.); (Z.S.)
| | - Andrea Rossnerova
- Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague, Czech Republic;
| | - Zuzana Simova
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague, Czech Republic; (M.S.); (Z.S.)
| | - Pavel Rossner
- Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague, Czech Republic; (M.S.); (Z.S.)
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Wen Q, Wang Y, Li X, Jin X, Wang G. Decreased serum exosomal miR-29a expression and its clinical significance in papillary thyroid carcinoma. J Clin Lab Anal 2020; 35:e23560. [PMID: 33368640 PMCID: PMC7843262 DOI: 10.1002/jcla.23560] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 12/19/2022] Open
Abstract
Background Aberrant levels of circulating microRNAs (miRNAs) are potential biomarkers in papillary thyroid carcinoma (PTC) diagnosis and therapy. The aim of this study was to evaluate serum exosomal miR‐29a expression as a non‐invasive biomarker for PTC diagnosis and prognosis. Methods Quantitative reverse transcription polymerase chain reaction was applied to measure serum exosomal miR‐29a expression levels in blood samples of 119 patients with PTC and 100 control subjects. Results Serum exosomal miR‐29a expression levels were significantly decreased in PTC cases. In addition, receiver operating characteristic (ROC) analysis revealed serum exosomal miR‐29a could well differentiate PTC from normal controls. Moreover, serum exosomal miR‐29a levels increased progressively and significantly 30 days and 90 days after surgery. Furthermore, PTC patients with lower serum exosomal miR‐29a expression had higher risk of recurrence. Decreased serum exosomal miR‐29a expression was significantly associated with worse clinical variables including tumor size, extrathyroidal extension, and TNM stage, as well as shorter survival. Finally, both univariate and multivariate identified serum exosomal miR‐29a as an independent prognostic indicator for overall survival. Conclusion These results demonstrated that serum exosomal miR‐29a might serve as a potential biomarker for PTC diagnosis and prognosis.
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Affiliation(s)
- Qiuting Wen
- Department of Pathology, Qiqihar Medical University, Qiqihar, China
| | - Yulou Wang
- Department of General Surgery, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, China
| | - Xingjiang Li
- Department of General Surgery, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, China
| | - Xiangguo Jin
- Department of General Surgery, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, China
| | - Guimei Wang
- Department of General Surgery, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, China
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Guo J, Zhu Z, Zhang D, Chen B, Zou B, Gao S, Zhu X. Analysis of the differential expression profile of miRNAs in myocardial tissues of rats with burn injury. Biosci Biotechnol Biochem 2020; 84:2521-2528. [PMID: 32867589 DOI: 10.1080/09168451.2020.1807901] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Fifteen percent third-degree burn rat model was used to identify miRNAs that are markers of burn injury-induced myocardial damage. Cardiac tissues were evaluated to determine miRNA profile sequencing. Pearson's correlation analysis was used between miRNAs and injury markers. ROC curve analysis was used to estimate miRNA's sensitivity and specificity for the diagnosis of myocardial damage caused by burn injury. The sequencing analysis revealed 23 differentially expressed miRNAs. Pearson's correlation analysis revealed that rno-miR-190b-3p and C5b9, rno-miR-341, rno-miR-344b-3p and TnI, rno-miR-344b-3p and CK-MB were significantly positively correlated, respectively. ROC curve analysis demonstrated that rno-miR-341, rno-miR-344b-3p, and rno-miR-190b-3p exhibited high sensitivity and specificity for the diagnosis of myocardial damage caused by burn injury. In conclusion, our results suggest that rno-miR-341, rno-miR-344b-3p, and rno-miR-190b-3p have the potential to be used as sensitive and specific biomarkers to diagnose myocardial damage caused by burn injury.
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Affiliation(s)
- Jingdong Guo
- The Department of Plastic and Burn Surgery, Shenzhen Hospital, Southern Medical University , Shenzhen, China.,The Third School of Clinical Medicine, Southern Medical University , Shenzhen, China
| | - Zhensen Zhu
- The Department of Plastic and Burn Surgery, Shenzhen Hospital, Southern Medical University , Shenzhen, China.,The Third School of Clinical Medicine, Southern Medical University , Shenzhen, China
| | - Dongmei Zhang
- The Department of Plastic and Burn Surgery, Shenzhen Hospital, Southern Medical University , Shenzhen, China.,The Third School of Clinical Medicine, Southern Medical University , Shenzhen, China
| | - Bo Chen
- The Department of Plastic and Burn Surgery, Shenzhen Hospital, Southern Medical University , Shenzhen, China.,The Third School of Clinical Medicine, Southern Medical University , Shenzhen, China
| | - Ben Zou
- The Department of Plastic and Burn Surgery, Shenzhen Hospital, Southern Medical University , Shenzhen, China.,The Third School of Clinical Medicine, Southern Medical University , Shenzhen, China
| | - Songying Gao
- The Department of Plastic and Burn Surgery, Shenzhen Hospital, Southern Medical University , Shenzhen, China.,The Third School of Clinical Medicine, Southern Medical University , Shenzhen, China
| | - Xiongxiang Zhu
- The Department of Plastic and Burn Surgery, Shenzhen Hospital, Southern Medical University , Shenzhen, China.,The Third School of Clinical Medicine, Southern Medical University , Shenzhen, China
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Mukherjee M, Goswami S. Global cataloguing of variations in untranslated regions of viral genome and prediction of key host RNA binding protein-microRNA interactions modulating genome stability in SARS-CoV-2. PLoS One 2020; 15:e0237559. [PMID: 32780783 PMCID: PMC7418985 DOI: 10.1371/journal.pone.0237559] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 07/29/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The world is going through the critical phase of COVID-19 pandemic, caused by human coronavirus, SARS-CoV-2. Worldwide concerted effort to identify viral genomic changes across different sub-types has identified several strong changes in the coding region. However, there have not been many studies focusing on the variations in the 5' and 3' untranslated regions and their consequences. Considering the possible importance of these regions in host mediated regulation of viral RNA genome, we wanted to explore the phenomenon. METHODS To have an idea of the global changes in 5' and 3'-UTR sequences, we downloaded 8595 complete and high-coverage SARS-CoV-2 genome sequence information from human host in FASTA format from Global Initiative on Sharing All Influenza Data (GISAID) from 15 different geographical regions. Next, we aligned them using Clustal Omega software and investigated the UTR variants. We also looked at the putative host RNA binding protein (RBP) and microRNA binding sites in these regions by 'RBPmap' and 'RNA22 v2' respectively. Expression status of selected RBPs and microRNAs were checked in lungs tissue. RESULTS We identified 28 unique variants in SARS-CoV-2 UTR region based on a minimum variant percentage cut-off of 0.5. Along with 241C>T change the important 5'-UTR change identified was 187A>G, while 29734G>C, 29742G>A/T and 29774C>T were the most familiar variants of 3'UTR among most of the continents. Furthermore, we found that despite the variations in the UTR regions, binding of host RBP to them remains mostly unaltered, which further influenced the functioning of specific miRNAs. CONCLUSION Our results, shows for the first time in SARS-Cov-2 infection, a possible cross-talk between host RBPs-miRNAs and viral UTR variants, which ultimately could explain the mechanism of escaping host RNA decay machinery by the virus. The knowledge might be helpful in developing anti-viral compounds in future.
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Affiliation(s)
- Moumita Mukherjee
- National Institute of Biomedical Genomics, Kalyani, West Bengal, India
| | - Srikanta Goswami
- National Institute of Biomedical Genomics, Kalyani, West Bengal, India
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Grillone K, Riillo C, Scionti F, Rocca R, Tradigo G, Guzzi PH, Alcaro S, Di Martino MT, Tagliaferri P, Tassone P. Non-coding RNAs in cancer: platforms and strategies for investigating the genomic "dark matter". J Exp Clin Cancer Res 2020; 39:117. [PMID: 32563270 PMCID: PMC7305591 DOI: 10.1186/s13046-020-01622-x] [Citation(s) in RCA: 145] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 06/11/2020] [Indexed: 12/18/2022] Open
Abstract
The discovery of the role of non-coding RNAs (ncRNAs) in the onset and progression of malignancies is a promising frontier of cancer genetics. It is clear that ncRNAs are candidates for therapeutic intervention, since they may act as biomarkers or key regulators of cancer gene network. Recently, profiling and sequencing of ncRNAs disclosed deep deregulation in human cancers mostly due to aberrant mechanisms of ncRNAs biogenesis, such as amplification, deletion, abnormal epigenetic or transcriptional regulation. Although dysregulated ncRNAs may promote hallmarks of cancer as oncogenes or antagonize them as tumor suppressors, the mechanisms behind these events remain to be clarified. The development of new bioinformatic tools as well as novel molecular technologies is a challenging opportunity to disclose the role of the "dark matter" of the genome. In this review, we focus on currently available platforms, computational analyses and experimental strategies to investigate ncRNAs in cancer. We highlight the differences among experimental approaches aimed to dissect miRNAs and lncRNAs, which are the most studied ncRNAs. These two classes indeed need different investigation taking into account their intrinsic characteristics, such as length, structures and also the interacting molecules. Finally, we discuss the relevance of ncRNAs in clinical practice by considering promises and challenges behind the bench to bedside translation.
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Affiliation(s)
- Katia Grillone
- Laboratory of Translational Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
| | - Caterina Riillo
- Laboratory of Translational Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
- Medical and Translational Oncology Units, AOU Mater Domini, 88100 Catanzaro, Italy
| | - Francesca Scionti
- Laboratory of Translational Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
| | - Roberta Rocca
- Laboratory of Translational Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
- Net4science srl, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
| | - Giuseppe Tradigo
- Laboratory of Bioinformatics, Department of Medical and Surgical Sciences, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
| | - Pietro Hiram Guzzi
- Laboratory of Bioinformatics, Department of Medical and Surgical Sciences, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
| | - Stefano Alcaro
- Net4science srl, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
- Department of Health Sciences, Magna Græcia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
| | - Maria Teresa Di Martino
- Laboratory of Translational Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
- Medical and Translational Oncology Units, AOU Mater Domini, 88100 Catanzaro, Italy
| | - Pierosandro Tagliaferri
- Laboratory of Translational Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
- Medical and Translational Oncology Units, AOU Mater Domini, 88100 Catanzaro, Italy
| | - Pierfrancesco Tassone
- Laboratory of Translational Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, 88100 Catanzaro, Italy
- Medical and Translational Oncology Units, AOU Mater Domini, 88100 Catanzaro, Italy
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Long S, Ren D, Zhong F, Niu Y, Qin X, Mu D, Liu W. Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145. PeerJ 2020; 8:e9337. [PMID: 32587801 PMCID: PMC7304417 DOI: 10.7717/peerj.9337] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 05/20/2020] [Indexed: 12/16/2022] Open
Abstract
Objective To analyze the expression levels of miR-145 in ALL children and their effects on the prognosis of ALL and to explore the mechanism of miR-145 in reversing the resistance of ALL cells to glucocorticoids. Methods A GEO database dataset was used to analyze the expression levels of miR-145 in ALL children. The association between miR-145 and childhood prognosis was analyzed by the TARGET database data. The expression levels of miR-145 in the glucocorticoid-resistant ALL cell line CEM-C1 were increased by lipofectamine 2000-mediated transfection. Cell proliferation inhibition experiments were performed to detect the effect of miR-145 on the response of CEM-C1 cell line to glucocorticoids. The expression levels of the apoptotic, autophagic and drug resistance-associated genes and proteins were detected by qPCR and western blot analysis. Results The expression levels of miR-145 were decreased in ALL patients (P < 0.001) and the prognosis of ALL in children with high miR-145 expression was significantly improved (P < 0.001). Increased miR-145 expression can improve the sensitivity of CEM-C1 cells to glucocorticoids. The expression levels of the proapoptotic and the anti-apoptotic genes Bax and Bcl-2 were increased and decreased, respectively, whereas the expression levels of the autophagicgenes Beclin 1 and LC were increased. In addition, the expression levels of the drug resistance gene MDR1 were decreased. Conclusion The expression levels of miR-145 in ALL children were decreased and they were associated with disease prognosis. The data indicated that miR-145 can reverse cell resistance by regulating apoptosis of CEM-C1 cells and autophagy.
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Affiliation(s)
- Sili Long
- Department of Pediatrics, Affiliated Hospital of Southwest Medical University, Children's Blood and Tumor PI laboratory, Birth Defects Clinical Medical Research Center of Sichuan Province, Luzhou, China
| | - Danwei Ren
- Department of Pediatrics, Affiliated Hospital of Southwest Medical University, Children's Blood and Tumor PI laboratory, Birth Defects Clinical Medical Research Center of Sichuan Province, Luzhou, China
| | - Fangfang Zhong
- Department of Pediatrics, Affiliated Hospital of Southwest Medical University, Children's Blood and Tumor PI laboratory, Birth Defects Clinical Medical Research Center of Sichuan Province, Luzhou, China
| | - Yana Niu
- Department of Pediatrics, Affiliated Hospital of Southwest Medical University, Children's Blood and Tumor PI laboratory, Birth Defects Clinical Medical Research Center of Sichuan Province, Luzhou, China
| | - Xiang Qin
- Department of Pediatrics, Affiliated Hospital of Southwest Medical University, Children's Blood and Tumor PI laboratory, Birth Defects Clinical Medical Research Center of Sichuan Province, Luzhou, China
| | - Dan Mu
- Department of Pediatrics, Affiliated Hospital of Southwest Medical University, Children's Blood and Tumor PI laboratory, Birth Defects Clinical Medical Research Center of Sichuan Province, Luzhou, China
| | - Wenjun Liu
- Department of Pediatrics, Affiliated Hospital of Southwest Medical University, Children's Blood and Tumor PI laboratory, Birth Defects Clinical Medical Research Center of Sichuan Province, Luzhou, China
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Minezaki T, Usui Y, Asakage M, Takanashi M, Shimizu H, Nezu N, Narimatsu A, Tsubota K, Umazume K, Yamakawa N, Kuroda M, Goto H. High-Throughput MicroRNA Profiling of Vitreoretinal Lymphoma: Vitreous and Serum MicroRNA Profiles Distinct from Uveitis. J Clin Med 2020; 9:jcm9061844. [PMID: 32545709 PMCID: PMC7356511 DOI: 10.3390/jcm9061844] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/06/2020] [Accepted: 06/09/2020] [Indexed: 01/01/2023] Open
Abstract
Purpose: Vitreoretinal lymphoma (VRL) is a non-Hodgkin lymphoma of the diffuse large B cell type (DLBCL), which is an aggressive cancer causing central nervous system related mortality. The pathogenesis of VRL is largely unknown. The role of microRNAs (miRNAs) has recently acquired remarkable importance in the pathogenesis of many diseases including cancers. Furthermore, miRNAs have shown promise as diagnostic and prognostic markers of cancers. In this study, we aimed to identify differentially expressed miRNAs and pathways in the vitreous and serum of patients with VRL and to investigate the pathogenesis of the disease. Materials and Methods: Vitreous and serum samples were obtained from 14 patients with VRL and from controls comprising 40 patients with uveitis, 12 with macular hole, 14 with epiretinal membrane, 12 healthy individuals. The expression levels of 2565 miRNAs in serum and vitreous samples were analyzed. Results: Expression of the miRNAs correlated significantly with the extracellular matrix (ECM) ‒receptor interaction pathway in VRL. Analyses showed that miR-326 was a key driver of B-cell proliferation, and miR-6513-3p could discriminate VRL from uveitis. MiR-1236-3p correlated with vitreous interleukin (IL)-10 concentrations. Machine learning analysis identified miR-361-3p expression as a discriminator between VRL and uveitis. Conclusions: Our findings demonstrate that aberrant microRNA expression in VRL may affect the expression of genes in a variety of cancer-related pathways. The altered serum miRNAs may discriminate VRL from uveitis, and serum miR-6513-3p has the potential to serve as an auxiliary tool for the diagnosis of VRL.
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Affiliation(s)
- Teruumi Minezaki
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
| | - Yoshihiko Usui
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
- Correspondence:
| | - Masaki Asakage
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
| | - Masakatsu Takanashi
- Department of Molecular Pathology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (M.T.); (M.K.)
| | - Hiroyuki Shimizu
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
| | - Naoya Nezu
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
| | - Akitomo Narimatsu
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
| | - Kinya Tsubota
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
| | - Kazuhiko Umazume
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
| | - Naoyuki Yamakawa
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
| | - Masahiko Kuroda
- Department of Molecular Pathology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (M.T.); (M.K.)
| | - Hiroshi Goto
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; (T.M.); (M.A.); (H.S.); (N.N.); (A.N.); (K.T.); (K.U.); (N.Y.); (H.G.)
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Cao Z, Qiu J, Yang G, Liu Y, Luo W, You L, Zheng L, Zhang T. MiR-135a biogenesis and regulation in malignancy: a new hope for cancer research and therapy. Cancer Biol Med 2020; 17:569-582. [PMID: 32944391 PMCID: PMC7476096 DOI: 10.20892/j.issn.2095-3941.2020.0033] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 05/27/2020] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that affect posttranscriptional regulation by binding to the 3′-untranslated region of target messenger RNAs. MiR-135a is a critical miRNA that regulates gene expression, and many studies have focused on its function in cancer research. MiR-135a is dysregulated in various cancers and regulates cancer cell proliferation and invasion via several signaling pathways, such as the MAPK and JAK2/STAT3 pathways. MiR-135a has also been found to promote or inhibit the epithelial-mesenchymal transition and chemoresistance in different cancers. Several studies have discovered the value of miR-135a as a novel biomarker for cancer diagnosis and prognosis. These studies have suggested the potential of therapeutically manipulating miR-135a to improve the outcome of cancer patients. Although these findings have demonstrated the role of miR-135a in cancer progression and clinical applications, a number of questions remain to be answered, such as the dual functional roles of miR-135a in cancer. In this review, we summarize the available studies regarding miR-135a and cancer, including background on the biogenesis and expression of miR-135a in cancer and relevant signaling pathways involved in miR-135a-mediated tumor progression. We also focus on the clinical application of miR-135a as a biomarker in diagnosis and as a therapeutic agent or target in cancer treatment, which will provide a greater level of insight into the translational value of miR-135a.
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Affiliation(s)
- Zhe Cao
- Department of General Surgery
| | | | | | | | | | - Lei You
- Department of General Surgery
| | - Lianfang Zheng
- Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Taiping Zhang
- Department of General Surgery.,Clinical Immunology Center, Chinese Academy of Medical Sciences, Beijing 100730, China
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He Q, Fang Y, Lu F, Pan J, Wang L, Gong W, Fei F, Cui J, Zhong J, Hu R, Liang M, Fang L, Wang H, Yu M, Zhang ZF. Analysis of differential expression profile of miRNA in peripheral blood of patients with lung cancer. J Clin Lab Anal 2019; 33:e23003. [PMID: 31541491 PMCID: PMC6868404 DOI: 10.1002/jcla.23003] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 07/19/2019] [Accepted: 07/23/2019] [Indexed: 12/26/2022] Open
Abstract
PURPOSE To identify potential molecular targets for lung cancer intervention and diagnosis, we analyzed the differential miRNA expression of peripheral blood between lung cancer patients and healthy controls. METHODS Three pairs of cases' and controls' peripheral blood samples were evaluated for miRNA expression by microarray. 12 miRNAs were selected for RT-PCR validation and target genes prediction. In addition, 4 miRNAs were selected for future validation by RT-PCR in a large sample of 145 cases and 55 frequency-matched healthy controls. RESULTS A total of 338 differentially expressed miRNAs were screened and identified by microarray. According to the fold changes, the top ten upregulated miRNAs were hsa-miR-124-3p, hsa-miR-379-5p, hsa-miR-3655, hsa-miR-450b-5p, hsa-miR-29a-5p, hsa-miR-200a-3p, hsa-miR-542-3p, hsa-miR-138-5p, hsa-miR-219a-2-3p, and hsa-miR-4701-3p, and the top ten downregulated miRNAs were hsa-miR-34c-5p, hsa-miR-135a-5p, hsa-miR-132-3p, hsa-miR-3178, hsa-miR-4449, hsa-miR-4999-3p, hsa-miR-1246, hsa-miR-4424, hsa-miR-1252-5p, and hsa-miR-24-2-5p. RT-PCR verification of the 12 miRNAs revealed that 5 of 8 upregulated miRNAs, 2 of 4 downregulated miRNAs showed a significant difference between the cases and controls (P < .05). A large number of target genes and their functional set showed overlapping among the 453 predicted target genes of the 12 miRNAs (P < .01). RT-PCR in the large sample confirmed the significant differential expression level of hsa-miR-29a-5p, hsa-miR-135a-5p, hsa-miR-542-3p, and hsa-miR-4491 between cases and controls (P < .05), and three of these microRNA, except hsa-miR-29a-5p, were significant after Bonferroni correction for adjustment of multiple comparisons. CONCLUSION There was a significant difference in miRNAs expression in the peripheral blood between lung cancer patients and healthy controls, and 4 miRNAs were validated by a large-size sample.
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Affiliation(s)
- Qingfang He
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Yirong Fang
- Shaoxing Center for Disease Control and Prevention, Shaoxing, China
| | - Feng Lu
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Jin Pan
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Lixin Wang
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Weiwei Gong
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Fangrong Fei
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | | | - Jieming Zhong
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Ruying Hu
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Mingbin Liang
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Le Fang
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Hao Wang
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Min Yu
- Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou, China
| | - Zuo-Feng Zhang
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA
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