MicroRNA-7 inhibits colorectal cancer cell proliferation, migration and invasion via TYRO3 and phosphoinositide 3-kinase/protein B kinase/mammalian target of rapamycin pathway suppression

作者：Qin, Ancheng; Qian, Weifeng^*

来源：International Journal of Molecular Medicine, 2018, 42(5): 2503-2514.

DOI：10.3892/ijmm.2018.3864

• microRNA-7
• TYRO3
• colorectal cancer
• proliferation
• migration
• invasion
• phosphoinositide 3-kinase
• protein kinase B
• mammalian target of rapamycin pathway

MicroRNA-7 (miR-7) is a non-coding RNA that inhibits colorectal cancer (CRC) cell proliferation, migration and invasion. miR-7 effectively silences TYRO3 expression, and the close association between TYRO3 and CRC has previously been reported. Therefore, the present study aimed to assess the roles and molecular mechanisms of TYRO3 and miR-7 in the development of CRC. The expression levels of miR-7 and TYRO3 in CRC tissues and cell lines were detected by reverse transcription-quantitative polymerase chain reaction. A dual-luciferase reporter assay was also performed to confirm whether TYRO3 was a target of miR-7. The effect of miR-7 and TYRO3 on cell proliferation, migration and invasion was detected in vitro with MTT, wound healing and cell invasion assays, respectively. The expression of proteins associated with the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was detected by western blot analysis. The results indicated that the expression of miR-7 was downregulated and the levels of TYRO3 were gradually increased in CRC tissues and cell lines. TYRO3 was identified as a functional target of miR-7, and its expression was negatively regulated by miR-7 in CRC cell lines. The functional studies demonstrated that miR-7 knockdown promoted the proliferation, migration and invasion of CRC cells, while knockdown of TYRO3 repressed these biological processes. In addition, pathway analyses revealed that the oncogenic effect of TYRO3 was associated with PI3K/AKT/mTOR pathway inhibition. In conclusion, the data suggested that miR-7 promoted the development of CRC by targeting oncogenic TYRO3, which may be mediated by inhibition of the PI3K/AKT/mTOR signaling pathway. Thus, miR-7 may serve as an independent prognostic biomarker in patients with CRC.

• 出版日期2018-11
• 单位南京医科大学