microRNA-520f inhibits hepatocellular carcinoma cell proliferation and invasion by targeting TM4SF1.

microRNAs (miRNAs) are reported to play crucial roles in tumorigenesis. Dysregulation of miR-520f has been implicated to be involved in several cancer progressions. However, the biological functions of miR520f in hepatocellular carcinoma (HCC) remain unclear. Thus, the molecular mechanism underlying miR-520f on HCC development was investigated in this study. Here, we found that miR-520f was remarkably down-regulated in human HCC samples and cell lines compared to paired normal tissues and cell lines as detected by qRT-PCR. Furthermore, the deregulated miR-520f was strongly associated with larger tumor size, advanced TNM stage, and metastasis in HCC patients. Functional investigations revealed that overexpression of miR-520f significantly suppressed cell proliferation, invasion and migration, caused cell cycle arrested at G0/G1 phase, and promoted cell apoptosis in HCC cells according to MTT, colony formation, transwell, and flow cytometry assays, respectively, whereas, downregulation of miR-520f exhibited inverse effects. Transmembrane-4 L-Six family member-1 (TM4SF1) was identified as a direct target of miR-520f, and an inverse relationship was found between miR-520f and TM4SF1 mRNA levels in HCC specimens. Rescue experiments suggested that restoration of TM4SF1 partially abolished miR-520f-meidated cell proliferation and invasion inhibition in HCC cells through regulating P13K/AKT and p38 MAPK signaling pathways. In conclusion, these data indicated that miR-520f acted as tumor suppressor in HCC proliferation and invasion by targeting TM4SF1, which might provide potential therapeutic evidence for HCC patients.

Du X ，Fan W ，Chen Y 《-》

MicroRNA-655-3p functions as a tumor suppressor by regulating ADAM10 and β-catenin pathway in Hepatocellular Carcinoma.

Wu G ，Zheng K ，Xia S ，Wang Y ，Meng X ，Qin X ，Cheng Y ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer.

Park YR ，Lee ST ，Kim SL ，Liu YC ，Lee MR ，Shin JH ，Seo SY ，Kim SH ，Kim IH ，Lee SO ，Kim SW ... -  《-》

MiRNA-206 suppresses PGE2-induced colorectal cancer cell proliferation, migration, and invasion by targetting TM4SF1.

MiRNA (miR)-206 plays a tumor suppressor role in various cancer types. Here, we investigated whether miR-206 is involved in prostaglandin E2 (PGE2)-induced epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC) cells through the targetting of transmembrane 4 L six family member 1 (TM4SF1).The effect of PGE2 on growth and apoptosis of CRC cells was evaluated using the MTT assay and flow cytometry analysis, respectively. TM4SF1 and miR-206 expression levels were determined with quantitative polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The concentration of PGE2 in the serum of CRC patients and healthy controls was measured with an ELISA kit. A miR-206 or TM4SF1 construct was transfected into cells with PGE2. Transwell migration and invasion assays were used to examine cell migration and invasion properties. Additionally, a luciferase assay was performed to determine whether TM4SF1 was directly targetted by miR-206.We found that miR-206 was down-regulated and TM4SF1 was up-regulated in human CRC tissues and cell lines. Moreover, miR-206 was negatively correlated with TM4SF1 expression. Bioinformatics analysis and a luciferase reporter assay revealed that miR-206 directly targetted the 3'-untranslated region (UTR) of TM4SF1, and TM4SF1 expression was reduced by miR-206 overexpression at both the mRNA and protein levels. Additionally, PGE2 significantly suppressed the expression of miR-206 and increased the expression of TM4SF1 in CRC cells. PGE2 induction led to enhanced CRC cell proliferation, migration, and invasion. Moreover, the overexpression of miR-206 decreased CRC cell proliferation, migration, and invasion compared with control group in PGE2-induced cells, and these effects could be recovered by the overexpression of TM4SF1. Overexpression of miR-206 also suppressed the expression of β-catenin, VEGF, MMP-9, Snail, and Vimentin and enhanced E-cadherin expression in PGE2-induced cells. These results could be reversed by the overexpression of TM4SF1. At last, up-regulation of miR-206 suppressed expression of p-AKT and p-ERK by targetting TM4SF1 in PGE2-induced cells.Our results provide further evidence that miR-206 has a protective effect on PGE2-induced colon carcinogenesis.

Park YR ，Seo SY ，Kim SL ，Zhu SM ，Chun S ，Oh JM ，Lee MR ，Kim SH ，Kim IH ，Lee SO ，Lee ST ，Kim SW ... -  《-》

MicroRNA-451: epithelial-mesenchymal transition inhibitor and prognostic biomarker of hepatocelluar carcinoma.

Huang JY ，Zhang K ，Chen DQ ，Chen J ，Feng B ，Song H ，Chen Y ，Zhu Z ，Lu L ，De W ，Wang R ，Chen LB ... -  《Oncotarget》