MiR-3653 inhibits the metastasis and epithelial-mesenchymal transition of colon cancer by targeting Zeb2.

Aberrant expression of microRNAs (miRNAs) has been widely recognized to play critical roles in the pathogenic processes of colon cancer. However, the expression and functions of miR-3653 in colon cancer remain uncovered. This study revealed for the first time that miR-3653 expression was significantly decreased in colon cancer tissues and cell lines. MiR-3653 overexpression led to decreased migration and invasion of HCT116 cells while miR-3653 knockdown resulted in opposite influence of the metastatic behaviors of HT29 cells. qRT-PCR and western blot demonstrated that miR-3653 suppressed the epithelial-mesenchymal transition (EMT) of colon cancer cells using both gain- and loss- of function assay. Mechanically, miR-3653 was found to interact with the 3'-UTR of Zeb2 through the complementary sequences and inhibited the expression of Zeb2 in colon cancer cells. Rescue experiments demonstrated that the inhibitory effect of miR-3653 overexpression on cell metastasis and EMT was abrogated by forced expression of Zeb2. This study demonstrates that miR-3653 suppresses the metastasis and EMT of colon cells by targeting Zeb2, and serves as a promising biomarker and therapeutic target in colon cancer.

Zhu W ，Luo X ，Fu H ，Liu L ，Sun P ，Wang Z ... -  《-》

miR-124 regulates EMT based on ZEB2 target to inhibit invasion and metastasis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis. MicroRNAs (miRNAs) serve a role in promoting and suppressing tumors in various types of malignant cancer, including TNBC. However, the regulatory mechanism of miR-124 in TNBC has still remains unclear. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-124. Cell viability was analyzed with CCK-8 assay. Cell colony formation ability was detected with colony formation assay. Cell invasion was measured with transwell assay. Dual luciferase reporter assay was conducted to verify whether ZEB2 is a target gene of miR-124. The mRNA and protein expression levels of ZEB2 and EMT markers were detected by quantitative real time PCR and western blot, respectively. Our results showed that miR-124 was down-regulated in TNBC tissues and cells. Overexpression of miR-124 inhibited the proliferation, metastasis and epithelial-mesenchymal transition (EMT) of TNBC cells. Furthermore, ZEB2 3'UTR was considered to be a direct target of miR-124 with luciferase reporter assay. Rescue experiments confirmed that EMT was regulated by miR-124 via suppression of ZEB2. miR-124 suppresses EMT and metastasis via ZEB2. Therefore, miR-124 may represent a potential therapeutic target for TNBC.

Ji H ，Sang M ，Liu F ，Ai N ，Geng C ... -  《-》

MicroRNA-377 Counteracts With Cancer Stem Cell Phenotypes and Epithelial Mesenchymal Transformation by Targeting ZEB2 in Colon Cancer.

Shayimu P ，Yusufu A ，Rehemutula A ，Redati D ，Jiapaer R ，Tuerdi R ... -  《-》

MiR-138-5p suppresses lung adenocarcinoma cell epithelial-mesenchymal transition, proliferation and metastasis by targeting ZEB2.

MiR-138-5p is regarded as a tumour suppressor in many cancers. Transforming growth factor beta (TGF-β) often acts as a tumor promotor at the late stages of human cancers. However, the function of miR-138-5p on lung adenocarcinoma cells induced by TGF-β remains to be further confirmed. RT-qPCR was used to detect the expression of human lung adenocarcinoma tissues, adjacent normal tissues, and relative cell lines. When the lung adenocarcinoma cells A549 and H1299 were transfected with negative control (NC), miR-138-5p mimics and miR-138-5p inhibitor by lipofectamine3000 and treated with or without TGF-β1, the lung adenocarcinoma cell function was detected by Immunofluorescence, Western blotting (WB), cell counting Kit-8 (CCK8), colony formation, EdU, Wound-healing and Transwell assays. The relation between miR-138-5p and zinc finger E-box-binding homeobox 2 (ZEB2) was detected by RT-qPCR, WB, and Luciferase reporter assays. When ZEB2 was knocked down, the lung adenocarcinoma cell function was detected by WB, CCK8 and Transwell assays. The expression of miR-138-5p was decreased in lung adenocarcinoma tissues and cell lines. When treated with or without TGF-β1, overexpression of miR-138-5p suppressed EMT, proliferation and metastasis of A549 and H1299. ZEB2 was verified as the direct target of miR-138-5p. Downregulation of ZEB2 suppressed EMT, proliferation and metastasis of lung adenocarcinoma cell, which could be reversed by miR-138-5p inhibitor. MiR-138-5p inhibits epithelial-mesenchymal transition, growth and metastasis of lung adenocarcinoma cells through targeting ZEB2.

Zhu D ，Gu L ，Li Z ，Jin W ，Lu Q ，Ren T ... -  《-》

MicroRNA-200c Inhibits the Metastasis of Triple-Negative Breast Cancer by Targeting ZEB2, an Epithelial-Mesenchymal Transition Regulator.

Triple-negative breast cancer (TNBC) is one of the most common malignant, highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-200c, play an important role in various types of malignant cancer, including TNBC. However, the biological role of miRNA-200c in TNBC is not well understood. In this study, we investigated the mechanism of miR-200c in the growth of TNBC. Reverse transcription quantitative polymerase chain reaction was used to detect the expression of miR-200c in TNBC tissues and TNBC cells. Cell Counting Kit-8 (CCK-8) assays, wound healing, and transwell assays were used to observe the effects of miR-200c on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers were detected by Western blotting. Dual luciferase reporter assays were used to test whether ZEB2 is a novel target of miR-200c. Our results show that ZEB2 is a novel target of miR-200c and that ZEB2 mediates the metastasis of triple-negative breast cancer via EMT. miR-200c attenuates TNBC cell invasion and EMT by targeting ZEB2. Our data therefore suggest that miR-200c may be used to develop novel early-stage diagnostic and therapeutic strategies for TNBC.

Chen H ，Li Z ，Zhang L ，Zhang L ，Zhang Y ，Wang Y ，Xu M ，Zhong Q ... -  《-》