miR-1285 Restrains Gastric Cancer Cell Growth and Causes Apoptosis by Negatively Regulating RAB1A
CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION(2022)
摘要
MicroRNAs (miRNAs) act as critical biological factors in gastric cancer (GC). miR-1285 has been ascertained as a crucial antioncogene in some cancers. However, the effect of miR-1285 in GC and the regulatory mechanism are not clear. In this study, we revealed that miR-1285 expression was significantly reduced in GC. Overexpressing miR-1285 restrained GC cell multiplication and accelerated apoptosis, whereas suppressing miR-1285 facilitated cell growth and restrained apoptosis. The level of miR-1285 was negatively related to the RAB1A level in GC tissue specimens. RAB1A was verified by reporter gene assay as a target of miR-1285. Overexpression of miR-1285 suppressed the RAB1A level, whereas suppression of miR-1285 promoted the level of RAB1A expression. Knockdown of RAB1A resulted in analogical biological effect as that caused by overexpressing miR-1285. Moreover, both miR-1285 overexpression and RAB1A knockdown led to suppression of the mTOR/S6K1 pathway. By contrast, inhibition of miR-1285 promoted the mTOR/S6K1 pathway. In addition, miR-1285 also regulated the Bcl-2/Bax pathway. Taken together, our data indicate that miR-1285 suppresses GC cell multiplication by restraining the mTOR/S6K1 pathway and induces cell apoptosis by regulating the Bcl-2/Bax pathway via modulating RAB1A.
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关键词
miR-1285, gastric cancer, RAB1A, cell multiplication, S6K1 signaling pathway
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