The miR-155-5p/FBXO11 axis inhibits the progression of gastric cancer via the mTOR pathway.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-related death. MicroRNAs (miRNAs or miRs) play a crucial role in the pathology of GC, including cell proliferation, invasion, and metastasis. In this study, genes targeted by miR-155-5p were predicted using bioinformatic tools. We found that the expression of miR-155-5p in GC cell lines differed relative to the expression of F-box protein 11 (FBXO11), which is involved in the regulation of cellular processes. This study sought to examine the function of miR-155-5p and the precise mechanism underlying its regulatory function in modulating proliferation and apoptosis in GC. METHODS: The luciferase reporter assay results showed that miR-155-5p bound directly to the three prime untranslated region (3'-UTR) of FBXO11, which further downregulated FBXO11 expression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western-blot analyses confirmed that miR-155-5p negatively regulated the messenger RNA (mRNA) and protein expression of FBXO11. The effects of FBXO11 on cell proliferation and apoptosis in GC cell lines was further examined using Cell Counting Kit-8 (CCK-8) and flow cytometry. RESULTS: We found that FBXO11 promoted proliferation and decreased apoptosis in GC cells. Conversely, rescue experiments showed that the knockdown of FBXO11 limited the effects of miR-155-5p on the proliferation and apoptosis of GC cells, providing further evidence that FBXO11 is a functional target of miR-155-5p. Further, the overexpression of miR-155-5p inhibited cell growth via the targeted inhibition of FBXO11 that regulated mammalian target of rapamycin (mTOR) signaling pathway in the GC cells. CONCLUSIONS: Overall, these results showed that miR-155-5p may serve as a tumor suppressor in GC and that the miR-155-5p/FBXO11 axis regulates tumor progression via the mTOR signaling pathway. Consequently, our findings may lead to the development a novel treatment strategy for GC.