MicroRNA-4268 inhibits cell proliferation via AKT/JNK signalling pathways by targeting Rab6B in human gastric cancer.

Abstract

MicroRNAs (miRNAs) play critical roles in the tumorigenesis and progression of gastric cancer (GC). However, the biological function of miR-4268 in GC and its mechanism remain unclear. In the present study, qTR-PCR found that the expression of miR-4268 was significantly downregulated in GC tissues and cell lines. The overexpression of miR-4268 inhibited GC cell proliferation and the cell cycle G1/S phase transition, and induced cell apoptosis. In contrast, inhibition of miR-4268 promoted cell proliferation and G1-S transition, and suppressed cell apoptosis. Further analyses revealed that miR-4268 expression was negatively correlated with Rab6B expression in GC tissues. Rab6B was verified to be a direct target of miR-4268. Notably, silencing Rab6B resulted in the same biological effects in GC cells as those induced by overexpression of miR-4268. Importantly, both miR-4268 overexpression and Rab6B silence inhibited the AKT/JNK signaling pathways, which modulated cell cycle regulators (Cyclin D1 and CDK4). In contrast, inhibition of miR-4268 promoted the AKT/JNK signaling pathways. MiR-4268 overexpression also promoted the p38 MAPK signaling pathway. Taken together, miR-4268 suppresses GC cell proliferation through inhibiting the AKT/JNK signaling pathways by targeting Rab6B and induces cell apoptosis through promoting the p38 MAPK signaling pathway. Our findings indicate a tumor-suppressor role of miR-4268 in GC pathogenesis and the potential of miR-4268 in GC theropy.

• Authors: Lingyu Zhao, Meng Xue, Lu Zhang, Bo Guo, Yannan Qin, Qiuyu Jiang, Ruifang Sun, Juang Yang, Lumin Wang, Liying Liu, Xiaofei Wang, Chen Huang, Dongdong Tong
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 27 Issue 6 Pg. 461-472 (06 2020) ISSN: 1476-5500 [Electronic] England
• PMID: 31303644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Rab6 protein
• Proto-Oncogene Proteins c-akt
• rab GTP-Binding Proteins

Topics

• Apoptosis (physiology)
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Humans
• MAP Kinase Signaling System
• Middle Aged
• Proto-Oncogene Proteins c-akt (metabolism)
• Stomach Neoplasms (genetics, metabolism, pathology)
• Transfection
• rab GTP-Binding Proteins (genetics, metabolism)