• cancer
• molecular biology

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/metabolism
• Lung Neoplasms/pathology
• Neovascularization, Pathologic/genetics
• Gene Expression Regulation, Neoplastic
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/metabolism
• Carcinoma, Non-Small-Cell Lung/pathology
• Male
• Smoke/adverse effects
• Female
• Animals
• Smoking/adverse effects

• R00 HL098695 NHLBI NIH HHS
• R01 HL155948 NHLBI NIH HHS
• R01CA225977 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
• PR211314 U.S. Department of Defense (United States Department of Defense)
• U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
• U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)

• Cancer therapeutics
• Chemosensitivity
• Immunoregulation
• MiR-1
• MiRNAs

• AD = adenocarcinoma
• AUC-ROC curve = area under the receiver operating characteristics curve
• BSC = best supportive care
• CEA = carcinoembryonic antigen
• CYFRA21-1 = cytokeratin 19 fragment 21-1
• ICIs = immune checkpoint inhibitors
• LCC = large cell carcinoma
• LC = lung cancer
• LDCT = low-dose CT
• NSCLC = non–small cell lung cancer
• PBMC = peripheral blood mononuclear cell
• PD-1 = programmed cell death-1
• PD-L1 = programmed cell death-ligand 1
• PET = positron emission tomography
• PNs = pulmonary nodules
• SCC = squamous cell carcinoma antigen
• SCLC = small cell lung cancer
• SQ = squamous cell carcinoma
• TMB = tumor mutation burden
• ddPCR = droplet digital PCR

• LINC01518
• PIK3CA/Akt pathway
• apoptosis
• miR-1-3p
• oesophageal squamous cell carcinoma
• proliferation

Triple-negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Previous studies have demonstrated that some abnormal expression of non-coding RNAs including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely related to tumor cell proliferation, apoptosis, invasion, migration and drug sensitivity. However, the role of non-coding RNAs in the pathogenesis of TNBC is still unclear. In order to characterize the molecular mechanism of non-coding RNAs in TNBC, we downloaded RNA data and miRNA data from the cancer genome atlas database. We successfully identified 686 message RNAs (mRNAs), 26 miRNAs and 50 lncRNAs as key molecules for high risk of TNBC. Then, we hypothesized that the lncRNA–miRNA–mRNA regulatory axis positively correlates with TNBC and constructed a competitive endogenous RNA (ceRNA) network of TNBC. Our series of analyses has shown that five molecules (TERT, TRIML2, PHBP4, mir-1-3p, mir-133a-3p) were significantly associated with the prognosis of TNBC, and there is a prognostic ceRNA sub-network between those molecules. We mapped the Kaplan–Meier curve of RNA on the sub-network and also suggested that the expression level of the selected RNA is related to the survival rate of breast cancer. Reverse transcription-quantitative polymerase chain reaction showed that the expression level of TRIML2 in TNBC cells was higher than normal. In general, our findings have implications for predicting metastasis, predicting prognosis and discovering new therapeutic targets for TNBC.

• Survival prognosis
• Triple-negative breast cancer
• ceRNA network

Tumor metastasis is a hallmark of cancer, with distant metastasis frequently developing in lung cancer, even at initial diagnosis, resulting in poor prognosis and high mortality. However, available biomarkers cannot reliably predict cancer spreading sites. The metastatic cascade involves highly complicated processes including invasion, migration, angiogenesis, and epithelial-to-mesenchymal transition that are tightly controlled by various genetic expression modalities along with interaction between cancer cells and the extracellular matrix. In particular, microRNAs (miRNAs), a group of small non-coding RNAs, can influence the transcriptional and post-transcriptional processes, with dysregulation of miRNA expression contributing to the regulation of cancer metastasis. Nevertheless, although miRNA-targeted therapy is widely studied in vitro and in vivo, this strategy currently affords limited feasibility and a few miRNA-targeted therapies for lung cancer have entered into clinical trials to date. Advances in understanding the molecular mechanism of metastasis will thus provide additional potential targets for lung cancer treatment. This review discusses the current research related to the role of miRNAs in lung cancer invasion and metastasis, with a particular focus on the different metastatic lesions and potential miRNA-targeted treatments for lung cancer with the expectation that further exploration of miRNA-targeted therapy may establish a new spectrum of lung cancer treatments.

• epithelial-to-mesenchymal transition
• lung cancer
• metastasis
• microRNA

MicroRNAs (miRNAs), which are endogenous short noncoding RNAs, can regulate genes involved in important biological and pathological functions. Therefore, dysregulation of miRNAs plays a critical role in cancer progression. However, whether the aberrant expression of miRNAs is regulated by oncogenes remains unclear. We previously demonstrated that a disintegrin and metalloprotease domain 9 (ADAM9) promotes lung metastasis by enhancing the expression of a pro-migratory protein, CUB domain containing protein 1 (CDCP1). In this study, we found that this process occurred via miR-1 down-regulation. miR-1 expression was down-regulated in lung tumors, but increased in ADAM9-knockdown lung cancer cells, and was negatively correlated with CDCP1 expression as well as the migration ability of lung cancer cells. Luciferase-based reporter assays showed that miR-1 directly bound to the 3′-untranslated region of CDCP1 and inhibited its translation. Treatment with a miR-1 inhibitor restored CDCP1 protein levels and enhanced tumor cell mobility. Overexpression of miR-1 decreased tumor metastases and increased the survival rate in mice. ADAM9 knockdown reduced EGFR signaling and increased miR-1 expression. These results revealed that ADAM9 down-regulates miR-1 via activating EGFR signaling pathways, which in turn enhances CDCP1 expression to promote lung cancer progression.

• ADAM9
• CDCP1
• EGFR
• lung cancer
• miR-1

For the purpose of demonstrating the clinical value and unraveling the molecular mechanisms of micro RNA (miR)-1-3p in colorectal carcinoma (CRC), the present study collected expression and diagnostic data from Gene Expression Omnibus (GEO), ArrayExpress and existing literature to conduct meta-analyses and diagnostic tests. Furthermore, the potential targets of miR-1-3p were attained from datasets that transfected miR-1-3p into CRC cells, online prediction databases and differentially expressed genes from The Cancer Genome Atlas and literature. Subsequently, bioinformatics analysis was conducted based on the aforementioned selected target genes. As a result, downregulation of miR-1-3p was observed. The combined standardized mean difference was −0.51 with 95% confidence interval (CI) of −0.68 to −0.33 using a fixed effect model, which demonstrated a significant downregulation of miR-1-3p in CRC. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio diagnostic score and odds ratio were 0.74 (95%CI: 0.48, 0.90), 0.75 (95%CI: 0.35, 0.94), 2.94 (95%CI: 1.01, 8.55), 0.34 (95%CI: 0.19, 0.60), 2.15 (95%CI: 1.06, 3.23) and 8.57 (95%CI: 2.89, 25.36). The summarized receiver operating characteristic curve demonstrated that the area under the curve was 0.81. In bioinformatics analyses based on 30 promising targets, the most enriched terms in Gene Ontology were positive regulation of transcription from RNA polymerase II promoter, extracellular region and transcription factor binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis highlighted the pathway termed cytokine-cytokine receptor interaction. In protein-protein interaction analysis, platelet factor 4 was selected as the hub gene. To conclude, miR-1-3p is downregulated in CRC and likely suppresses CRC via multiple biological approaches, which indicates the diagnostic potential and tumor suppressive efficacy.

• Angiogenesis
• Gastric cancer
• Vascular endothelial growth factor A
• miR-1

• Adenocarcinoma/genetics
• Adenocarcinoma/pathology
• Adult
• Aged
• Endothelin-1/biosynthesis
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Genes, Tumor Suppressor
• Humans
• Male
• MicroRNAs/genetics
• Middle Aged
• Neovascularization, Pathologic/genetics
• Stomach Neoplasms/genetics
• Stomach Neoplasms/pathology
• Vascular Endothelial Growth Factor A/biosynthesis

• LW29 Beijing Cancer Hospital
• ZLYX201701 Administration of Hospitals Clinical Medicine Development of Special Funding Support
• 81374016 National Natural Science Foundation of China (CN)
• D141100000414002 Beijing Municipal Science and Technology Commission
• Beijing Municipal Science and Technology Commission

• angiogenesis
• lung cancer
• microRNA-1
• tumor microenvironment
• vascular endothelial growth factor blockers

Dysregulation of microRNAs in various types of human cancer promote or suppress oncogenesis. MicroRNA (miR)-1 was previously revealed to function as a tumor suppressor in prostate cancer cells, and its expression was associated with reduced metastatic potential in lung cancer. The present study investigated the role of miR-1 and its association with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) in the pathophysiology of esophageal squamous cell carcinoma (ESCC), and analyzed the effects of miR-1 inhibitor or mimics on sensitivity to epidermal growth factor receptor-tyrosine kinase inhibitors, the alterations of cell cycle distribution and apoptosis in ESCC cells. Compared with normal tissues, the level of miR-1 expression was significantly lower and PIK3CA expression was higher in ESCC tissues. The level of miR-1 expression was also inversely associated with the level of PIK3CA mRNA expression. Low miR-1 and high PIK3CA expression levels were strongly associated with lymph node metastasis, and the level of miR-1 expression was negatively associated with clinical Tumor-Node-Metastasis stage. Furthermore, exogenous expression of miR-1 inhibited growth, arrested cell cycle in the G₁ phase and increased apoptosis in ESCC cells, whereas it decreased PIK3CA protein expression levels. Furthermore, overexpression of miR-1 increased the sensitivity of ESCC cells to the anticancer drug, gefitinib. A possible mechanism for this increased sensitivity to gefitinib may be inactivation of the PIK3CA signaling pathway. To the best of our knowledge, this is the first time that the results of the present study demonstrated that miR-1 upregulation may be a potential strategy for the treatment of human ESCC.

• esophageal squamous cell carcinoma
• gefitinib
• microRNA-1
• phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α
• tumor suppressor

• immunohistochemistry
• nasopharyngeal carcinoma
• phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α
• rho-associated coiled-coil-containing protein kinase 1
• tissue microarray

• Cigarette-smoke (CS)
• estrogen
• lung cancer (LC)
• microRNA (miRNA)

• Biomarker
• Cancer
• Cellular response
• Resistance
• microRNA-1

• EBVaGC
• JAK2
• PD-L1
• PD-L2
• PIK3CA

• LASP1
• TAGLN2
• esophageal squamous cell carcinoma
• microRNA-1

MicroRNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of miRNAs is an important factor in the development and progression of disease. The canonical myomiRs (miR-1, -133 and -206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomiR expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomiRs at the crossroads between cell development/tissue regeneration/tissue inflammation responses, and cancer development.

• Muscle microRNAs
• MiR-1
• MiR-206
• MiR-133a
• MiR-133b
• Cell development
• Cancer

• R01 AA022701 NIAAA NIH HHS

• Gastric cancer
• Non-coding RNA
• Target therapy
• Tumor suppressor gene
• miR-1

There is an increased risk of developing ovarian cancer (OC) in patients with endometriosis. Hence, development of new biomarkers may provide a positive clinical outcome for early detection. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in biological and pathological process and are currently used as diagnostic and prognostic markers in various cancers. In the current study, we assessed the differential expression of miRNAs from 19 paired ovarian cancer and its associated endometriosis tissue samples. In addition we also analyzed the downstream targets of those miRNAs.

Nineteen paired cases of ovarian cancer and endometriosis foci were identified by a gynecologic pathologist and macro-dissected. The total RNAs were extracted and subjected to comprehensive miRNA profiling from the pooled samples of these two different entities using microarray analysis. Later, the abnormal expressions of few selected miRNAs were validated in individual cases by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed target mRNAs which were validated by qRT-PCR.

The miRNA profiling identified deregulation of greater than 1156 miRNAs in OC, of which the top seven were further validated by qRT-PCR. The expression of miR-1, miR-133a, and miR-451 were reduced significantly (p<0.0001) in the OC patients compared to its associated endometriosis. In contrast, the expression of miR-141, miR-200a, miR-200c, and miR-3613 were elevated significantly (p<0.05) in most of the OC patients. Furthermore, among the downstream mRNAs of these miRNAs, the level of PTEN expression was significantly (p<0.05) reduced in OC compared to endometriosis while no significant difference was observed in NF-κB expression.

The expression of miRNAs and mRNAs in OC were significantly different compared to its concurrent endometriosis. These differential expressed miRNAs may serve as potential diagnostic and prognostic biomarkers for OC associated with endometriosis.

• Endometriosis
• FFPE
• NF-κB
• Ovarian cancer
• PTEN
• miRNA

While the mechanisms of human cancer development are not fully understood, evidence of microRNA (miRNA, miR) dysregulation has been reported in many human diseases, including cancer. miRs are small noncoding RNA molecules that regulate posttranscriptional gene expression by binding to complementary sequences in the specific region of gene mRNAs, resulting in downregulation of gene expression. Not only are certain miRs consistently dysregulated across many cancers, but they also play critical roles in many aspects of cell growth, proliferation, metastasis, apoptosis, and drug resistance. Recent studies from our group and others revealed that miR-1 is frequently downregulated in various types of cancer. Through targeting multiple oncogenes and oncogenic pathways, miR-1 has been demonstrated to be a tumor suppressor gene that represses cancer cell proliferation and metastasis and promotes apoptosis by ectopic expression. In this review, we highlight recent findings on the aberrant expression and functional significance of miR-1 in human cancers and emphasize its significant values for therapeutic potentials.