Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell lung cancer

Abstract

Abstract. Lung cancer is the most frequent cause of mortality in cancer patients; non-small-cell lung cancer (NSCLC) accounts for ~80% of lung cancer cases. MicroRNAs (miRNAs) have been revealed to perform an important role in cancer development and progression. Based on a custom miRNA microarray analysis of patients with NSCLC, miRNA-615-3p (miR-615-3p) downregulation was identified in NSCLC tissues compared with normal lung tissues, which suggested that miR-615-3p acted as a tumor suppressor in lung cancer. The overexpression of miR-615-3p was then validated using 40 pairs of NSCLC and adjacent normal tissue samples using a TaqMan reverse transcription-quantitative polymerase chain reaction assay. In order to investigate the tumor suppressor function of miR-615-3p, the ectopic expression of miR-615-3p in the NSCLC A549, H1299 and H1650 cell lines was established. The results revealed that overexpressed miR-615-3p markedly inhibited cell proliferation and colony formation in the 3 NSCLC cell lines compared with the cells overexpressing the negative control sequence (NC). Additional investigation revealed that miR-615-3p overexpression significantly induced apoptosis and cell cycle arrest at the G1 phase in the A549, H1299 and H1650 cell lines compared with the cells overexpressing NC. Finally, ectopic expression of miR-615-3p was found to repress the cell migration and invasion of the 3 lung cancer cell lines. The results of the present study demonstrate, for the first time, that miR-615-3p functions as a tumor suppressor in NSCLC, and may be a novel potential molecular therapeutic target for patients with NSCLC.

MicroRNA‑615‑5p regulates the proliferation and apoptosis of breast cancer cells by targeting HSF1

“…In addition, bioinformatic analysis predicted that HSF1 was a target gene of microRNA-615-5p, which was confirmed by a dual luciferase reporter assay. The present study is consistent with previous studies, which demonstrated that microRNA-615-5p functions as a tumor suppressor (12), whereas HSF1 serves as a tumor promoter (13).…”

Elevated miR-615-3p Expression Predicts Adverse Clinical Outcome and Promotes Proliferation and Migration of Prostate Cancer Cells

“…In contrast, in nonesmall-cell lung cancer, miR-615-3p expression has been identified as down-regulated in tumor samples compared with normal tissue samples and to inhibit cell proliferation and migration in vitro. 34 The seeming discrepancy in regard to the role of miR-615-3p as either an oncomiRNA or a tumor suppressor in different malignancies indicates that miR-615-3p functions in a highly cell-and disease-typeespecific manner. This may be explained, at least in part, by differences in target genes, as has previously been demonstrated for many other miRNAs.…”

microRNAs Mediated Regulation of the Ribosomal Proteins and its Consequences on the Global Translation of Proteins

“…While, miR-615-3p plays important role in the differentiation of cells, it suppresses GDF5 and FOXO1 and inhibits osteogenesis in the lumbar ligamentum flavum cells [ 269 ], it is also known to have a feed-forward loop with HOXC5, and repress hTERT during the differentiation of cells [ 270 ]. In cancer, miR-615-3p plays a dual role depending on the type, for example, it promotes gastric cancer potentially by targeting CELF2 [ 176 ] and prostate cancer [ 177 ], but reported to be a suppressor of NSCLC potentially targeting IGF2 [ 178 , 179 ] and esophageal cancer [ 180 ]. In addition, it could be used as a biomarker for the recurrent HCC [ 181 ] and also regulates lipoapoptosis by targeting the C/EBP homolog in mice [ 271 ].…”