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Borowczyk M, Dobosz P, Szczepanek-Parulska E, Budny B, Dębicki S, Filipowicz D, Wrotkowska E, Oszywa M, Verburg FA, Janicka-Jedyńska M, Ziemnicka K, Ruchała M. Follicular Thyroid Adenoma and Follicular Thyroid Carcinoma-A Common or Distinct Background? Loss of Heterozygosity in Comprehensive Microarray Study. Cancers (Basel) 2023; 15:638. [PMID: 36765597 PMCID: PMC9913827 DOI: 10.3390/cancers15030638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 01/16/2023] [Accepted: 01/18/2023] [Indexed: 01/22/2023] Open
Abstract
Pre- and postsurgical differentiation between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC) represents a significant diagnostic challenge. Furthermore, it remains unclear whether they share a common or distinct background and what the mechanisms underlying follicular thyroid lesions malignancy are. The study aimed to compare FTA and FTC by the comprehensive microarray and to identify recurrent regions of loss of heterozygosity (LOH). We analyzed formalin-fixed paraffin-embedded (FFPE) samples acquired from 32 Caucasian patients diagnosed with FTA (16) and FTC (16). We used the OncoScan™ microarray assay (Affymetrix, USA), using highly multiplexed molecular inversion probes for single nucleotide polymorphism (SNP). The total number of LOH was higher in FTC compared with FTA (18 vs. 15). The most common LOH present in 21 cases, in both FTA (10 cases) and FTC (11 cases), was 16p12.1, which encompasses many cancer-related genes, such as TP53, and was followed by 3p21.31. The only LOH present exclusively in FTA patients (56% vs. 0%) was 11p11.2-p11.12. The alteration which tended to be detected more often in FTC (6 vs. 1 in FTA) was 12q24.11-q24.13 overlapping FOXN4, MYL2, PTPN11 genes. FTA and FTC may share a common genetic background, even though differentiating rearrangements may also be detected.
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Affiliation(s)
- Martyna Borowczyk
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
- Department of Medical Simulation, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Paula Dobosz
- Department of Genetics and Genomics, Central Clinical Hospital of the Ministry of Interior Affairs and Administration, 02-507 Warsaw, Poland
| | - Ewelina Szczepanek-Parulska
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Bartłomiej Budny
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Szymon Dębicki
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Dorota Filipowicz
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Elżbieta Wrotkowska
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Michalina Oszywa
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Frederik A. Verburg
- Department of Radiology and Nuclear Medicine, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands
| | | | - Katarzyna Ziemnicka
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Marek Ruchała
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
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Zhou Y, Dai X, Lyu J, Li Y, Bao X, Deng F, Liu K, Cui L, Cheng L. Construction and validation of a novel prognostic model for thyroid cancer based on N7-methylguanosine modification-related lncRNAs. Medicine (Baltimore) 2022; 101:e31075. [PMID: 36281116 PMCID: PMC9592387 DOI: 10.1097/md.0000000000031075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
BACKGROUND To construct and verify a novel prognostic model for thyroid cancer (THCA) based on N7-methylguanosine modification-related lncRNAs (m7G-lncRNAs) and their association with immune cell infiltration. METHODS In this study, we identified m7G-lncRNAs using co-expression analysis and performed differential expression analysis of m7G-lncRNAs between groups. We then constructed a THCA prognostic model, performed survival analysis and risk assessment for the THCA prognostic model, and performed independent prognostic analysis and receiver operating characteristic curve analyses to evaluate and validate the prognostic value of the model. Furthermore, analysis of the regulatory relationship between prognostic differentially expressed m7G-related lncRNAs (PDEm7G-lncRNAs) and mRNAs and correlation analysis of immune cells and risk scores in THCA patients were carried out. RESULTS We identified 29 N7-methylguanosine modification-related mRNAs and 116 differentially expressed m7G-related lncRNAs, including 87 downregulated and 29 upregulated lncRNAs. Next, we obtained 8 PDEm7G-lncRNAs. A final optimized model was constructed consisting of 5 PDEm7G-lncRNAs (DOCK9-DT, DPP4-DT, TMEM105, SMG7-AS1 and HMGA2-AS1). Six PDEm7G-lncRNAs (DOCK9-DT, DPP4-DT, HMGA2-AS1, LINC01976, MID1IP1-AS1, and SMG7-AS1) had positive regulatory relationships with 10 PDEm7G-mRNAs, while 2 PDEm7G-lncRNAs (LINC02026 and TMEM105) had negative regulatory relationships with 2 PDEm7G-mRNAs. Survival curves and risk assessment predicted the prognostic risk in both groups of patients with THCA. Forest maps and receiver operating characteristic curves were used to evaluate and validate the prognostic value of the model. Finally, we demonstrated a correlation between different immune cells and risk scores. CONCLUSION Our results will help identify high-risk or low-risk patients with THCA and facilitate early prediction and clinical intervention in patients with high risk and poor prognosis.
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Affiliation(s)
- Yang Zhou
- Department of Otolaryngology Head and Neck Surgery, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Xuezhong Dai
- Department of Otolaryngology Head and Neck Surgery, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Jianhong Lyu
- Department of Anesthesiology, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Yingyue Li
- Department of Otolaryngology Head and Neck Surgery, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Xueyu Bao
- Department of Otolaryngology Head and Neck Surgery, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Fang Deng
- Department of Otolaryngology Head and Neck Surgery, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Kun Liu
- Department of Otorhinolaryngology, Puren Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China
| | - Liming Cui
- Department of Otolaryngology Head and Neck Surgery, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, China
| | - Li Cheng
- Department of Endocrinology, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan, China
- * Correspondence: Li Cheng, The Third People’s Hospital of Yunnan Province, 292 Beijing Road, Guandu District, Kunming City, Yunnan Province 650011, China (e-mail: )
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Tong JY, Jiang W, Yu XQ, Wang R, Lu GH, Gao DW, Lv ZW, Li D. Effect of low-dose radiation on thyroid function and the gut microbiota. World J Gastroenterol 2022; 28:5557-5572. [PMID: 36304083 PMCID: PMC9594015 DOI: 10.3748/wjg.v28.i38.5557] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/21/2022] [Accepted: 09/07/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health; however, we know very little about the effects of low-dose ionizing radiation (LDR) on thyroid hormone levels and gut microbiota composition.
AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice.
METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay (ELISA), and stool samples were taken for 16S ribosomal RNA (rRNA) gene sequencing after irradiation.
RESULTS We found that LDR caused changes in thyroid stimulating hormone (TSH) levels in the irradiated mice, suggesting a dose-dependent response in thyroid function to ionizing radiation. No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls. The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls, and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups. And the abundances of uncultured_bacterium_g_Acinetobacter, uncultured_bacterium_ o_Mollicutes_RF39, uncultured_bacterium_g_Citrobacter, and uncultured_ bacterium_g_Lactococcus decreased in the radiated groups at the genus level, which showed a correlation with radiation exposure and diagnostic efficacy. Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities, such as nucleotide metabolism, carbohydrate metabolism, and glycan biosynthesis and metabolism. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions, including translation, replication and repair.
CONCLUSION LDR can change thyroid function and the gut microbiota, and changes in the abundances of bacteria are correlated with the radiation dose.
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Affiliation(s)
- Jun-Yu Tong
- Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Wen Jiang
- Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Xia-Qing Yu
- Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Ru Wang
- Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Gang-Hua Lu
- Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Ding-Wei Gao
- Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Zhong-Wei Lv
- Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Dan Li
- Department of Nuclear Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 200072, Guangdong Province, China
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Wang Y, Yue C, Yu Q, Yan L. Microarray analysis of molecules expressed during radiation-induced rat thyroid carcinogenesis. JOURNAL OF RADIATION RESEARCH 2021:rrab083. [PMID: 34632518 DOI: 10.1093/jrr/rrab083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Indexed: 06/13/2023]
Affiliation(s)
- Yuqing Wang
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250102, China
| | - Caixin Yue
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250102, China
| | - Qian Yu
- Center for Reproductive Medicine, Reproductive Hospital affiliated to Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250102, China
| | - Lei Yan
- School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250102, China
- Center for Reproductive Medicine, Reproductive Hospital affiliated to Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250102, China
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Matsuu-Matsuyama M, Shichijo K, Matsuda K, Fujimoto N, Kondo H, Miura S, Kurashige T, Nagayama Y, Nakashima M. Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid. Sci Rep 2021; 11:19096. [PMID: 34580369 PMCID: PMC8476610 DOI: 10.1038/s41598-021-98481-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 09/09/2021] [Indexed: 11/09/2022] Open
Abstract
Childhood radiation exposure is a known thyroid cancer risk factor. This study evaluated the effects of age on radiation-induced thyroid carcinogenesis in rats irradiated with 8 Gy X-rays. We analyzed cell proliferation, cell death, DNA damage response, and autophagy-related markers in 4-week-old (4W) and 7-month-old (7M) rats and the incidence of thyroid tumors in 4W, 4-month-old (4M), and 7M rats 18 months after irradiation. Cell death and DNA damage response were increased in 4W rats compared to those in controls at 1 month post-irradiation. More Ki-67-positive cells were observed in 4W rats at 12 months post-irradiation. Thyroid tumors were confirmed in 61.9% (13/21), 63.6% (7/11), and 33.3% (2/6) of irradiated 4W, 4M, and 7M rats, respectively, compared to 0%, 14.3% (1/7), and 16.7% (1/6) in the respective nonirradiated controls. There were 29, 9, and 2 tumors in irradiated 4W, 4M, and 7M rats, respectively. The expression of several autophagy components was downregulated in the area surrounding radiation-induced thyroid carcinomas in 4W and 7M rats. LC3 and p62 expression levels decreased in radiation-induced follicular carcinoma in 4W rats. Radiosensitive cells causing thyroid tumors may be more prevalent in young rats, and abrogation of autophagy may be associated with radiation-induced thyroid carcinogenesis.
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Affiliation(s)
- Mutsumi Matsuu-Matsuyama
- Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
| | - Kazuko Shichijo
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
| | - Katsuya Matsuda
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
| | - Nariaki Fujimoto
- Department of Disease Model, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan
| | - Hisayoshi Kondo
- Biostatistics Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
| | - Shiro Miura
- National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Ōmura, Nagasaki, 856-8562, Japan
| | - Tomomi Kurashige
- Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
| | - Yuji Nagayama
- Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
| | - Masahiro Nakashima
- Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
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Qiu K, Li K, Zeng T, Liao Y, Min J, Zhang N, Peng M, Kong W, Chen LL. Integrative Analyses of Genes Associated with Hashimoto's Thyroiditis. J Immunol Res 2021; 2021:8263829. [PMID: 34493981 PMCID: PMC8418929 DOI: 10.1155/2021/8263829] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/18/2021] [Accepted: 08/06/2021] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, is a common autoimmune thyroiditis, which mostly occurs in young and middle-aged women. It can be manifested as hyperthyroidism in the early stage; hypothyroidism may appear with the progression of the disease. Studies have shown that multiple factors such as heredity, environment, and autoimmunity are involved in the pathogenesis, but the specific mechanism is not clear. In our study, we tried to find key genes and potential molecular mechanisms of Hashimoto's thyroiditis to provide new ideas for the therapeutic targets of Hashimoto's thyroiditis. METHOD GSE138198 and GSE54958 were downloaded from the GEO database, and two datasets were combined for analysis. The combined data were normalized to identify the differentially expressed genes (DEGs), and GO and KEGG enrichment analyses were performed. Protein-protein interaction (PPI) networks and hub genes between DEGs were identified. We also used the miRWalk database to identify regulatory miRNAs associated with expressions of DEGs. RESULT We identified 182 DEGs (160 upregulated and 22 downregulated) between Hashimoto's disease patients and the healthy control group. GO analysis showed that DEGs were mostly concentrated in detection of chemical stimulus involved in sensory perception, intermediate filament cytoskeleton, and olfactory receptor activity. KEGG pathway analysis showed that DEGs were mainly related to olfactory transduction. Some members of the KRTAP family and HTR5A, KNG1, DRD3, HTR1D, TAS2R16, INSL5, TAS2R42, and GRM7 are the most important hub genes in the PPI network. In addition, we recognized that OTUD4, LLPH, and ECHDC1 were the most important hub genes in the miRNA-target gene network. CONCLUSION In this study, a series of bioinformatics analyses of DEGs were performed to identify the key genes and pathways associated with Hashimoto's thyroiditis. These genes and pathways provide a more detailed understanding of the pathogenesis of Hashimoto's disease and provide new ideas for the therapeutic targets of Hashimoto's thyroiditis.
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Affiliation(s)
- Kangli Qiu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan 430022, China
| | - Kai Li
- Network and Computing Center, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Tianshu Zeng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan 430022, China
| | - Yunfei Liao
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan 430022, China
| | - Jie Min
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan 430022, China
| | - Nan Zhang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan 430022, China
| | - Miaomiao Peng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan 430022, China
| | - Wen Kong
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan 430022, China
| | - Lu-lu Chen
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan 430022, China
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Lee SY, Kwon J, Lee KA. Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1. Oncol Rep 2021; 45:47. [PMID: 33649794 PMCID: PMC7934226 DOI: 10.3892/or.2021.7998] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 02/03/2021] [Indexed: 01/07/2023] Open
Abstract
Bcl2‑like‑10 (Bcl2l10) has both oncogenic and tumor suppressor functions depending on the type of cancer. It has been previously demonstrated that the suppression of Bcl2l10 in ovarian cancer SKOV3 and A2780 cells causes cell cycle arrest and enhances cell proliferation, indicating that Bcl2l10 is a tumor suppressor gene in ovarian cancer cells. The aim of the present study was to identify possible downstream target genes and investigate the underlying mechanisms of action of Bcl2l10 in ovarian cancer cells. RNA sequencing (RNA‑Seq) was performed to obtain a list of differentially expressed genes (DEGs) in Bcl2l10‑suppressed SKOV3 and A2780 cells. The RNA‑Seq data were validated by reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis, and the levels of metabolites after Bcl2l10‑knockdown were measured using colorimetric assay kits. Pathway enrichment analysis revealed that the commonly downregulated genes in SKOV3 and A2780 cells after Bcl2l10‑knockdown were significantly enriched in metabolic pathways. The analysis of the DEGs identified from RNA‑Seq and validated by RT‑qPCR revealed that succinate dehydrogenase complex subunit D (SDHD) and isocitrate dehydrogenase 1 (IDH1), which are key enzymes of the TCA cycle that regulate oncometabolite production, may be potential downstream targets of Bcl2l10. Furthermore, Bcl2l10‑knockdown induced the accumulation of succinate and isocitrate through the downregulation of SDHD and IDH1. The present study was the first to elucidate the metabolic regulatory functions of Bcl2l10 in ovarian cancer cells, and the results indicated that Bcl2l10 may serve as a potential therapeutic target in ovarian cancer.
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Affiliation(s)
- Su-Yeon Lee
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi 13488, Republic of Korea
| | - Jinie Kwon
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi 13488, Republic of Korea
| | - Kyung-Ah Lee
- Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi 13488, Republic of Korea,Correspondence to: Professor Kyung-Ah Lee, Department of Biomedical Science, College of Life Science, CHA University, 335 Pangyo-ro, Bundang, Seongnam, Gyeonggi 13488, Republic of Korea, E-mail:
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Therapeutic Effect of Mongolian Medicine RuXian-I on Hyperplasia of Mammary Gland Induced by Estrogen/Progesterone through CRYAB-Promoted Apoptosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:5707106. [PMID: 32595729 PMCID: PMC7273489 DOI: 10.1155/2020/5707106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 04/13/2020] [Accepted: 05/15/2020] [Indexed: 12/30/2022]
Abstract
The traditional Mongolian medicine (TMM) RuXian-I is an empirical formula specifically used for treating the hyperplasia of mammary gland (HMG) in clinic based on the principles of traditional Mongolian medicine, but the treatment mechanism is not completely clear. In this paper, we elaborated the mechanism of RuXian-I in the treatment of HMG induced by estrogen and progestogen from its toxicity and activity. Firstly, RuXian-I exhibited no toxic effect on HMG rats through no changes of body weight and food intake measurement and no pathologic changes of the organs (heart, liver, spleen, lung, and kidney) detected. Secondly, RuXian-I could decrease the increased nipple height and diameter and remarkably relieve the pathologic changes of HMG rats and also alleviate serum sex hormone levels (estradiol (E2), luteinizing hormone (LH), progesterone (P), and testosterone (T)) of HMG rats. Finally, RuXian-I could obviously inhibit the upregulation level of antiapoptotic protein CRYAB of HMG rats and promote mammary gland cell apoptosis of HMG rats via increases of promoting apoptosis protein caspases-3, 8, and 9 and Bax and tumor suppressor protein p53, decreases of antiapoptosis protein Bcl-2, and release of cytochrome c. These results suggested that RuXian-I has protective and therapeutic effects on HMG rats induced by estrogen and progestogen possibly via promoting apoptotic pathway regulated by CRYAB and is a promising agent for treating HMG.
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Zhang J, Liu J, Wu J, Li W, Chen Z, Yang L. Progression of the role of CRYAB in signaling pathways and cancers. Onco Targets Ther 2019; 12:4129-4139. [PMID: 31239701 PMCID: PMC6553995 DOI: 10.2147/ott.s201799] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 04/07/2019] [Indexed: 01/18/2023] Open
Abstract
CRYAB is a member of the small heat shock protein family, first discovered in the lens of the eye, and involved in various diseases, such as eye and heart diseases and even cancers, for example, breast cancer, lung cancer, prostate cancer, and ovarian cancer. In addition, CRYAB proteins are involved in a variety of signaling pathways including apoptosis, inflammation, and oxidative stress. This review summarizes the recent progress concerning the role of CRYAB in signaling pathways and diseases. Therefore, the role of CRYAB in signaling pathways and cancers is urgently needed. This article reviews the regulation of CRYAB in the apoptotic inflammatory signaling pathway and its role in cancers progression and as a key role in anti-cancer therapy targeting CRYAB in an effort to improve outcomes for patients with metastatic disease.
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Affiliation(s)
- JunFei Zhang
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, People's Republic of China
| | - Jia Liu
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, People's Republic of China
| | - JiaLi Wu
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, People's Republic of China
| | - WenFeng Li
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, People's Republic of China
| | - ZhongWei Chen
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, People's Republic of China
| | - LiShan Yang
- Department of Emergency Medical, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750000, People's Republic of China
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Donato L, Scimone C, Nicocia G, D'Angelo R, Sidoti A. Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis. Cell Cycle 2018; 18:84-104. [PMID: 30569795 DOI: 10.1080/15384101.2018.1558873] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Retinitis pigmentosa (RP) is a very heterogeneous inherited ocular disorder group characterized by progressive retinal disruption. Retinal pigment epithelium (RPE) degeneration, due to oxidative stress which arrests the metabolic support to photoreceptors, represents one of the principal causes of RP. Here, the role of oxidative stress in RP onset and progression was analyzed by a comparative whole transcriptome analysis of human RPE cells, treated with 100 µg/ml of oxLDL and untreated, at different time points. Experiment was thrice repeated and performed on Ion ProtonTM sequencing system. Data analysis, including low quality reads trimming and gene expression quantification, was realized by CLC Genomics Workbench software. The whole analysis highlighted 14 clustered "macro-pathways" and many sub-pathways, classified by selection of 5271 genes showing the highest alteration of expression. Among them, 23 genes were already known to be RP causative ones (15 over-expressed and 8 down-expressed), and their enrichment and intersection analyses highlighted new 77 candidate related genes (49 over-expressed and 28 down-expressed). A final filtering analysis then highlighted 29 proposed candidate genes. This data suggests that many new genes, not yet associated with RP, could influence its etiopathogenesis.
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Affiliation(s)
- Luigi Donato
- a Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine , University of Messina , Messina , Italy.,b Department of Cutting-Edge Medicine and Therapies, Biomolecular Strategies and Neuroscience, Section of Applied Neuroscience, Molecular Genetics and Predictive Medicine , I.E.ME.S.T. ., Palermo , Italy
| | - Concetta Scimone
- a Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine , University of Messina , Messina , Italy.,b Department of Cutting-Edge Medicine and Therapies, Biomolecular Strategies and Neuroscience, Section of Applied Neuroscience, Molecular Genetics and Predictive Medicine , I.E.ME.S.T. ., Palermo , Italy
| | - Giacomo Nicocia
- c Department of Clinical and Experimental Medicine , University of Messina , Messina , Italy
| | - Rosalia D'Angelo
- a Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine , University of Messina , Messina , Italy.,b Department of Cutting-Edge Medicine and Therapies, Biomolecular Strategies and Neuroscience, Section of Applied Neuroscience, Molecular Genetics and Predictive Medicine , I.E.ME.S.T. ., Palermo , Italy
| | - Antonina Sidoti
- a Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine , University of Messina , Messina , Italy.,b Department of Cutting-Edge Medicine and Therapies, Biomolecular Strategies and Neuroscience, Section of Applied Neuroscience, Molecular Genetics and Predictive Medicine , I.E.ME.S.T. ., Palermo , Italy
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Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings. Biosci Rep 2018; 38:BSR20180536. [PMID: 30061177 PMCID: PMC6200700 DOI: 10.1042/bsr20180536] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 07/21/2018] [Accepted: 07/26/2018] [Indexed: 12/19/2022] Open
Abstract
Uranium tailings (UT) are formed as a byproduct of uranium mining and are of potential risk to living organisms. In the present study, we sought to identify potential biomarkers associated with chronic exposure to low dose rate γ radiation originating from UT. We exposed C57BL/6J mice to 30, 100, or 250 μGy/h of gamma radiation originating from UT samples. Nine animals were included in each treatment group. We observed that the liver central vein was significantly enlarged in mice exposed to dose rates of 100 and 250 μGy/h, when compared with nonirradiated controls. Using proteomic techniques, we identified 18 proteins that were differentially expressed (by a factor of at least 2.5-fold) in exposed animals, when compared with controls. We chose glycine N-methyltransferase (GNMT), glutathione S-transferase A3 (GSTA3), and nucleophosmin (NPM) for further investigations. Our data showed that GNMT (at 100 and 250 μGy/h) and NPM (at 250 μGy/h) were up-regulated, and GSTA3 was down-regulated in all of the irradiated groups, indicating that their expression is modulated by chronic gamma radiation exposure. GNMT, GSTA3, and NPM may therefore prove useful as biomarkers of gamma radiation exposure associated with UT. The mechanisms underlying those changes need to be further studied.
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