PMID- 30849960 OWN - NLM STAT- MEDLINE DCOM- 20190621 LR - 20200225 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 19 IP - 1 DP - 2019 Mar 8 TI - MicroRNA-148b regulates tumor growth of non-small cell lung cancer through targeting MAPK/JNK pathway. PG - 209 LID - 10.1186/s12885-019-5400-3 [doi] LID - 209 AB - BACKGROUND: MicroRNA-148b (miR-148b) has been detected in various types of tumors, and is generally viewed as a tumor suppressor. Our previous study found the decreased expression of miR-148b in human non small cell lung cancer (NSCLC) specimens and cell lines. However, the underlying mechanisms of miR-148b in regulating tumor progression remain unclear. METHODS: Firstly animal experiments were performed to verify whether miR-148b could inhibit the tumor growth. Then, the underlying mechanisms were studied by transfecting recombinant plasmids containing a miR-148b mimic or a negative control (NC) mimic (shRNA control) into NSCLC cell lines PC14/B and A549 cells. Tumor cells transfected with unpackaged lentiviral vectors was used as blank control. Cell proliferation capabilities were measured by using CCK-8 kit and colony formation assay. Cell cycle arrest was compared to clarify the mechanism underlying the tumor cell proliferation. Annexin V-FITC Apoptosis Detection kit was applied to investigate the effect of miR-148b on cell apoptosis. Furthermore, western blot analysis were performed to study the targeting pathway. RESULTS: We found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiment showed that miR-148b inhibited tumor cell proliferation. Besides, over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing NSCLC cells from entering the mitotic phase and enhanced tumor cell apoptosis. Further western blot analysis indicated that miR148b could inhibit mitogen-activated protein kinase/Jun N-terminal kinase (MAPK/JNK) signaling by decreasing the expression of phosphorylated (p) JNK. CONCLUSIONS: These results demonstrate that miR-148b could inhibit the tumor growth and act as tumor suppressor by inhibiting the proliferation and inducing apoptosis of NSCLC cells by blocking the MAPK/JNK pathway. FAU - Lu, Lin AU - Lu L AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Liu, Qiyao AU - Liu Q AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Wang, Peipei AU - Wang P AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Wu, Yong AU - Wu Y AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Liu, Xia AU - Liu X AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Weng, Chengyin AU - Weng C AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Fang, Xisheng AU - Fang X AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Li, Baoxiu AU - Li B AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Cao, Xiaofei AU - Cao X AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Mao, Haibo AU - Mao H AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Wang, Lina AU - Wang L AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. FAU - Guan, Mingmei AU - Guan M AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. 13808815499@163.com. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. 13808815499@163.com. FAU - Wang, Wei AU - Wang W AD - Department of Experimental Research and State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, 510080, Guangdong, China. wangwei@sysucc.org.cn. FAU - Liu, Guolong AU - Liu G AUID- ORCID: 0000-0001-7391-8750 AD - Department of Medical Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China. eyglliu@scut.edu.cn. AD - Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China. eyglliu@scut.edu.cn. LA - eng GR - 81502563/National Natural Science Foundation of China/ GR - 81672900/National Natural Science Foundation of China/ GR - 2016A030310109/Natural Science Foundation of Guangdong Province/ GR - x2xy-D2175050/Fundamental Research Funds for the Central Universities/ GR - 201707010262/Science and Technology Program of Guangzhou/ PT - Journal Article DEP - 20190308 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (MIRN148 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Animals MH - Apoptosis/genetics MH - Carcinoma, Non-Small-Cell Lung/*genetics/*metabolism/pathology MH - Cell Cycle Checkpoints/genetics MH - Cell Line, Tumor MH - Cell Proliferation MH - Disease Models, Animal MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Lung Neoplasms/*genetics/*metabolism/pathology MH - *MAP Kinase Signaling System MH - Mice MH - MicroRNAs/*genetics MH - Phosphorylation MH - RNA Interference PMC - PMC6408859 OTO - NOTNLM OT - Apoptosis OT - MAPK/JNK pathway OT - Non small cell lung cancer (NSCLC);tumor suppressor OT - Proliferation OT - microRNA-148b COIS- ETHICS APPROVAL: The Ethics Committee of Guangzhou First People's Hospital approved all the animal experiments. This study did not involve in any human subjects or human material. The cell lines used in this study did not require ethics approval for the use. CONSENT FOR PUBLICATION: Not applicable COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/03/10 06:00 MHDA- 2019/06/22 06:00 PMCR- 2019/03/08 CRDT- 2019/03/10 06:00 PHST- 2018/09/25 00:00 [received] PHST- 2019/02/21 00:00 [accepted] PHST- 2019/03/10 06:00 [entrez] PHST- 2019/03/10 06:00 [pubmed] PHST- 2019/06/22 06:00 [medline] PHST- 2019/03/08 00:00 [pmc-release] AID - 10.1186/s12885-019-5400-3 [pii] AID - 5400 [pii] AID - 10.1186/s12885-019-5400-3 [doi] PST - epublish SO - BMC Cancer. 2019 Mar 8;19(1):209. doi: 10.1186/s12885-019-5400-3.