title: MicroRNA-1304 suppresses human non-small cell lung cancer cell growth in vitro by targeting heme oxygenase-1.
abstract: Previous studies have shown that microRNA-1304 (miR-1304) is dysregulated in certain types of cancers, including non-small cell lung cancer (NSCLC), and might be involved in tumor survival and/or growth. In this study we investigated the direct target of miR-1304 and its function in NSCLC in vitro. Human lung adenocarcinoma cell lines (A549 and NCI-H1975) were studied. The cell proliferation and survival were investigated via cell counting, MTT and colony-formation assays. Cell apoptosis and cell cycle were examined using annexin V-PE/7-AAD and PI staining assays, respectively. The dual-luciferase reporter assay was used to verify post-transcriptional regulation of heme oxygenase-1 (HO-1) by miR-1304. CRISPR/Cas9 was used to deplete endogenous miR-1304. Overexpression of MiR-1304 significantly decreased the number and viability of NSCLC cells and colony formation, and induced cell apoptosis and G0/G1phase cell cycle arrest. HO-1 was demonstrated to be a direct target of miR-1304 in NSCLC cells. Restoration of HO-1 expression by hemin (20 μmol/L) abolished the inhibition of miR-1304 on cell growth and rescued miR-1304-induced apoptosis in A549 cells. Suppression of endogenous miR-1304 with anti-1304 significantly increased HO-1 expression and promoted cell growth and survival in A549 cells. In 17 human NSCLC tissue samples, miR-1304 expression was significantly decreased, while HO-1 expression was significantly increased as compared to normal lung tissues. MicroRNA-1304 is a tumor suppressor and HO-1 is its direct target in NSCLC. The results suggest the potential for miR-1304 as a therapeutic target for NSCLC.
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Cheng-Gang
authors.initials: CG
authors.lastname: Li
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Meng-Fan
authors.initials: MF
authors.lastname: Pu
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chun-Zhu
authors.initials: CZ
authors.lastname: Li
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Man
authors.initials: M
authors.lastname: Gao
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Liu
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Cun-Zhi
authors.initials: CZ
authors.lastname: Yu
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Peng
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ze-Long
authors.initials: ZL
authors.lastname: Ma
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Qi
authors.affiliation: The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Yi-Zheng
authors.initials: YZ
authors.lastname: Wang
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Miao
authors.affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.|Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation
chemical_list: C575187:MIRN1304 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D006427:Hemin; D051547:Heme Oxygenase-1