MicroRNA-let-7a regulates cell autophagy by targeting Rictor in gastric cancer cell lines MGC-803 and SGC-7901

作者：Fan, Hao; Jiang, Mingkun; Li, Bowen; He, Yu; Huang, Chi; Luo, Dakui; Xu, Hao; Yang, Li^*; Zhou, Jundong^*

来源：Oncology Reports, 2018, 39(3): 1207-1214.

DOI：10.3892/or.2018.6194

• gastric cancer
• autophagy
• miR-let-7a
• Rictor
• mTOR

miR-let-7a is the most widely studied miRNA, whose functions have been well-established by scientists in both carcinogenesis and progression of human cancer, including gastric cancer (GC). However, to date there is a lack of information concerning the relationship between miR-let-7a and cellular autophagy. Using western blotting and immunofluorescence, we determined that upregulation of miR-let-7a led to increased cellular autophagic level, whereas miR-let-7a suppression decreased autophagy activity in GC cells. To further elucidate the mechanisms underlying this, we screened potential targets of miR-let-7a using bioinformatics analyses, validated by a series of assays. Our results indicated that Rptor independent companion of mTOR complex 2 (Rictor) was a direct target of miR-let-7a. In addition, rescue experiments in vitro showed that miR-let-7a promoted cellular autophagic level by inhibiting Rictor expression in GC cells. Furthermore, as an upstream executor of Akt-mTOR signaling pathway, we found that Rictor elaborated its effect on autophagy by phosphorylating Akt and mTOR, and this regulatory process could also be mediated by miR-let-7a. Taken together, our results present a novel role for miR-let-7a in GC which modulates autophagy by targeting Rictor, following the regulation of Akt-mTOR signal pathway.

• 出版日期2018-3
• 单位南京医科大学