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Published on: September 15, 2023
miR-1285 Restrains Gastric Cancer Cell Growth and Causes Apoptosis by Negatively Regulating RAB1A
Yali Lei1, Jing Chen2, Ning Wang1
1Department of Gastroenterology, Weinan Central Hospital, Weinan 714000, Shaanxi Province, China.
Abstract:
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.
Insights
MicroRNA 1285 (miR-1285) acts as an antioncogene in gastric cancer (GC). This study shows miR-1285 suppresses GC cell growth and promotes apoptosis by targeting RAB1A and regulating key cellular pathways.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are vital regulators in various cancers, including gastric cancer (GC).
- The specific role and regulatory mechanisms of miR-1285 in GC remain largely uncharacterized.
- Previous studies suggest miR-1285 functions as an antioncogene in other cancer types.
Purpose of the Study:
- To elucidate the function of miR-1285 in gastric cancer.
- To investigate the regulatory mechanism underlying miR-1285's action in GC.
- To identify the molecular targets and pathways modulated by miR-1285 in GC.
Main Methods:
- Quantitative real-time PCR to measure miR-1285 expression.
- Cell proliferation assays and apoptosis assays to assess cellular effects.
- Reporter gene assays to validate miR-1285 targets.
- Western blotting to analyze protein expression and pathway activation (mTOR/S6K1, Bcl-2/Bax).
Main Results:
- miR-1285 expression was significantly downregulated in GC tissues and cell lines.
- Overexpression of miR-1285 inhibited GC cell proliferation and induced apoptosis.
- miR-1285 directly targets RAB1A, and its knockdown mimicked the effects of miR-1285 overexpression.
- miR-1285, via RAB1A, suppressed the mTOR/S6K1 pathway and regulated the Bcl-2/Bax pathway.
Conclusions:
- miR-1285 acts as a tumor suppressor in gastric cancer.
- The miR-1285/RAB1A axis plays a critical role in regulating GC cell proliferation and apoptosis.
- Modulation of the mTOR/S6K1 and Bcl-2/Bax pathways by miR-1285 offers potential therapeutic targets for GC treatment.
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