Abstract
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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Conceptualization: Jiyun Cui and Dianjie Lin; Methodology: Jiyun Cui and Jing Wang; Formal analysis and investigation: Yuyao Shen; Writing - original draft preparation: Jiyun Cui, Jing Wang and Yuyao Shen; Writing - review and editing: Dianjie Lin; Approval of the manuscript: All authors.
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Jiyun Cui, Jing Wang, Yuyao Shen and Dianjie Lin declare that they have no conflict of interest.
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Cui, J., Wang, J., Shen, Y. et al. Suppression of HELLS by miR-451a represses mTOR pathway to hinder aggressiveness of SCLC. Genes Genom 43, 105–114 (2021). https://doi.org/10.1007/s13258-020-01028-1
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DOI: https://doi.org/10.1007/s13258-020-01028-1