Molecular mechanism of miR-153 inhibiting migration, invasion and epithelial-mesenchymal transition of breast cancer by regulating transforming growth factor beta (TGF-β) signaling pathway.

To investigate the role and mechanism of action of miR-153 in the migration, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-153 and transforming growth factor beta receptor 2 (TGFBR2) in tissue specimens and cells. miR-153 overexpression in breast cancer cells was achieved by miR-153 mimic transfection. Mobility and invasiveness of breast cancer cells were evaluated by transwell assay. EMT was evaluated by Western blot detecting the protein level of E-cadherin and Vimentin. Interaction of miR-153 and 3'-untranslated region (UTR) of TGFBR2 messenger RNA (mRNA) was investigated by luciferase reporter assay. The expression of miR-153 in breast cancer tissue specimens and MDA-MB-231 cells was significantly lower than that in nonmalignant counterparts, inversely correlating with that of TGFBR2 mRNA. Transfection with miR-153 mimic significantly increased miR-153 level in MDA-MB-231 cells while inhibiting its migration, invasion, and EMT in vitro, which could be mimicked by TGFBR2 knockdown. Luciferase reporter assay confirmed two targets of miR-153 on the 3'-UTR of TGFBR2 mRNA. Restoring TGFBR2 protein level by transient overexpression largely rescued migration, invasion, and EMT of MDA-MB-231 cells that were repressed by miR-153 mimic transfection. miR-153 inhibits breast cancer cell migration, invasion, and EMT by targeting TGFBR2.

Wang J ，Liang S ，Duan X 《-》

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 ... -  《-》

miR-300 inhibits epithelial to mesenchymal transition and metastasis by targeting Twist in human epithelial cancer.

Yu J ，Xie F ，Bao X ，Chen W ，Xu Q ... -  《Molecular Cancer》

Establishment of twist-1 and TGFBR2 as direct targets of microRNA-20a in mesenchymal to epithelial transition of breast cancer cell-line MDA-MB-231.

Messenchymal to epithelial transition (MET) is a significant physiological phenomenon involved in embryogenesis and cancer. This study aims at investigating the mechanism of microRNA-20a (miR-20a) mediated regulation of mesenchymal to epithelial transition and identification of its direct target genes in breast cancer cell-line, MDA-MB-231. Reduced migratory and invasive property, altered cellular morphology along with reduced capability for attachment to basement membrane was acquired by over-expression of miR-20a in invasive MDA-MB-231 cell-line initially expressing low level of this micro-RNA, indicating direct correlation between abundance of miR-20a and metastatic property. The switch from mesenchymal to epithelial cells mediated by miR-20a involved post-transcriptional down-regulation of twist1, which in turn controls downstream epithelial markers like E-cadherin, claudin and mesenchymal markers like N-cadherin, fibronectin, the crucial players of mesenchymal to epithelial transition (MET). Furthermore, another key component, TGF-β and one of its receptors (TGFBR2) were found to be down-regulated by miR-20a. Additionally, reporter assay established that post-transcriptional down-regulation of TGFBR2 occurred through direct binding of miR-20a to its 3'UTR, thus abrogating the TGF-β signaling pathway resulting in inhibition of MET. Delineating the underlying molecular mechanism of miR-20a-mediated MET and defining the target genes will help us to introduce a miRNA-mediated effective therapeutic strategy against breast cancer.

De S ，Das S ，Mukherjee S ，Das S ，Sengupta Bandyopadhyay S ... -  《-》