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KMID : 0381120210430020105
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Genes and Genomics
2021 Volume.43 No. 2 p.105 ~ p.114
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Suppression of HELLS by miR-451a represses mTOR pathway to hinder aggressiveness of SCLC
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Cui Jiyun
Wang Jing
Shen Yuyao
Lin Dianjie
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Abstract
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Background: Uncovering molecular pathogenesis and mechanisms of small cell lung cancer (SCLC) will contribute to SCLC therapy. Multiple studies demonstrated that miR-451a acts as an anti-tumor miRNA in non-small cell lung cancer. However, the mechanism of miR-451a in SCLC was ambiguous.
Objective: We aimed to explore the function of miR-451a in SCLC and decipher the underlying mechanisms.
Methods: TargetScan and dual-luciferase reporter assays were used to analyze the target genes of miR-451a. Cell counting kit-8 and colony formation assays were performed to assess the roles of miR-451a on cell growth. Gene set enrichment analysis (GSEA) was utilized to enrich biological pathways. Western blot was used to measure protein expression.
Results: MiR-451a expression was reduced dramatically in SCLC tissues and cell lines (NCI-H1688 and NCI-H446). Helicase, Lymphoid Specific (HELLS) was proved to be a target gene of miR-451a. In addition, cell proliferation assays in SCLC cells transfected with miR-451a mimic and/or HELLS revealed that miR-451a inhibited cell proliferation via targeting HELLS. Moreover, the roles of miR-451a/HELLS in expression of key proteins in mTOR and apoptosis signaling pathways suggested that miR-451a inactivated mTOR and activated apoptosis signaling pathway via directly silencing HELLS.
Conclusions: Our study indicated that miR-451a hinders SCLC cell proliferation in vitro through regulating mTOR and apoptosis signaling pathways via silencing HELLS, suggesting that miR-451a could be a promising tumor suppressor in SCLC. And there is a potential for miR-451a to be a drug target and biomarker for SCLC.
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KEYWORD
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Small cell lung cancer, miR-451a, Prognostic biomarker, Tumor suppressor
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