MiR-138 inhibits cell proliferation and reverses epithelial-mesenchymal transition in non-small cell lung cancer cells by targeting GIT1 and SEMA4C.

Non-small-cell lung cancer (NSCLC) is one of the most common and lethal malignant tumours worldwide with a poor 5-year survival rate. Recent studies indicated that miRNAs have been involved in the tumorigenic driver pathways in NSCLC, but the relevant molecular mechanisms are not well-understood. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in human NSCLC. The effects of miR-138 on the NSCLC cell growth and epithelial-mesenchymal transition (EMT) were first examined. Then the targeting connections of miR-138 with G-protein-coupled receptor kinase-interacting protein 1 (GIT1) and semaphorin 4C (SEMA4C) were confirmed by dual luciferase reporter assays. Finally, the effects of GIT1 and SEMA4C on the NSCLC cell growth and EMT were investigated respectively. We found that the ectopic expression of miR-138 resulted in a significant inhibition of NSCLC growth and reversion of EMT. GIT1 and SEMA4C were identified as two novel targets of miR-138. Furthermore, GIT1 and SEMA4C knockdown inhibited the cell growth and reversed EMT, just like the effects of miR-138 overexpression on NSCLC cells, whereas ectopic expression of GIT1 and SEMA4C partly rescued the suppressive effects of miR-138 in NSCLC cells. These data represent a crucial step towards the understanding of the novel roles and molecular mechanism of miR-138, GIT1 and SEMA4C in NSCLC progression, which may provide some new targets or prognostic biomarkers for NSCLC treatment, thus having implications in translational oncology.

Li J ，Wang Q ，Wen R ，Liang J ，Zhong X ，Yang W ，Su D ，Tang J ... -  《-》

UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC.

Jin D ，Guo J ，Wu Y ，Du J ，Wang X ，An J ，Hu B ，Kong L ，Di W ，Wang W ... -  《Theranostics》

MiR-145 and miR-203 represses TGF-β-induced epithelial-mesenchymal transition and invasion by inhibiting SMAD3 in non-small cell lung cancer cells.

MicroRNAs (miRNAs) have been proved to play important role in development of various cancers, including non-small cell lung cancer (NSCLC). Our previous studies have shown that miR-203 and miR-145 are associated with cellular invasion in NSCLC and nasopharyngeal cancer, respectively. However, the mechanistic role of miR-203 and miR-145 in TGF-β-induced epithelial-mesenchymal transition (EMT) has not yet been elucidated in human cancers, including NSCLC. Real-time quantitative reverse transcriptase PCR (qRT-PCR), western blot analysis, luciferase reporter gene assays, small RNA interference and transwell migration and invasion assays were carried on human NSCLC cell lines A549 and 95C. Thirty-six paired NSCLC tissues and adjacent noncancerous lung tissues were collected. Both miR-145 and miR-203 can directly target the 3'-untranslated region (3'-UTR) of SMAD3, and overexpression of the two miRNAs in NSCLC cells inhibited the expression of SMAD3 mRNA and protein, whereas inhibition of endogenous miR-145 or miR-203 caused an increased expression of SMAD3. Moreover, miR-145 and/or miR-203 repressed TGF-β-induced EMT and attenuated cell migration and invasion in A549 and 95C cells. siRNA-mediated knockdown of SMAD3 copied the phenotype of miR-145 and miR-203 overexpression in A549 and 95C cells. MiR-145 and miR-203 inhibited TGF-β-induced EMT and invasion through repression of SMAD3 in NSCLC cells. Our findings provided insights into the miRNA-based mechanism for controlling TGF-β-induced EMT of NSCLC cells and a strategy for targeted therapy of NSCLC.

Hu H ，Xu Z ，Li C ，Xu C ，Lei Z ，Zhang HT ，Zhao J ... -  《-》

Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p.

Lu W ，Zhang H ，Niu Y ，Wu Y ，Sun W ，Li H ，Kong J ，Ding K ，Shen HM ，Wu H ，Xia D ，Wu Y ... -  《Molecular Cancer》

MiR-182 inhibits the epithelial to mesenchymal transition and metastasis of lung cancer cells by targeting the Met gene.

The microRNA miR-182, belonging to the miR-183 family, is one of the most frequently studied cancer-related oncogenic miRNAs that is dysregulated in various cancer tissues, and it plays a crucial role in tumorigenesis and tumor progression. Studies revealed that miR-182 might function as an oncogenic or tumor suppressor miRNA in different tissues. However, the role of miR-182 in the development of lung cancer remains largely unknown. miR-182 expression in tumor samples from 58 patients, normal lung tissue samples, and lung cancer cell lines were evaluated by qRT-PCR. Survival curves were analyzed using the Kaplan-Meier method and compared with a log-rank test. Our study demonstrated that miR-182 is frequently downregulated in metastatic NSCLC cells compared with primary tumor tissues. Over-expression of miR-182 significantly inhibited the migration and invasion of lung cancer cells and promoted the expression of the epithelial marker (E-cadherin) in addition to reducing the levels of Snail in lung cancer cells. Further studies demonstrated that miR-182 negatively regulated Met via direct binding to the Met 3'-untranslated region (3'-UTR). Furthermore, we found that miR-182 suppressed the phosphorylation of AKT and the nuclear accumulation of Snail, a transcription factor that promotes the epidermal to mesenchymal transition (EMT). Moreover, miR-182 could repress cell migration, invasion, and EMT of lung cancer cells induced by hepatocyte growth factor (HGF). miR-182 might suppress the EMT and metastasis via inactivation of Met/AKT/Snail in non-small cell lung cancer (NSCLC) cells, which implicates miR-182 may be useful as a new therapeutic target in NSCLC.

Li Y ，Zhang H ，Li Y ，Zhao C ，Fan Y ，Liu J ，Li X ，Liu H ，Chen J ... -  《-》