Jiyun Cui1, Jing Wang1, Yuyao Shen2, Dianjie Lin3. 1. Department of Pulmonary and Critical Care Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250013, China. 2. Department of Pulmonary and Critical Care Medicine, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 26400, China. 3. Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, China. tulipcjy@163.com.
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.
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.
Entities:
Keywords:
Prognostic biomarker; Small cell lung cancer; Tumor suppressor; miR-451a
Authors: Lise Lotte Christensen; Anja Holm; Juha Rantala; Olli Kallioniemi; Mads H Rasmussen; Marie S Ostenfeld; Frederik Dagnaes-Hansen; Bodil Øster; Troels Schepeler; Heidi Tobiasen; Kasper Thorsen; Oliver M Sieber; Peter Gibbs; Philippe Lamy; Torben F Hansen; Anders Jakobsen; Eva M Riising; Kristian Helin; Jan Lubinski; Rikke Hagemann-Madsen; Søren Laurberg; Torben F Ørntoft; Claus L Andersen Journal: PLoS One Date: 2014-06-03 Impact factor: 3.240