title: Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer.
abstract: MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: The Second Department of Medical Oncology, Linyi Tumor Hospital, Linyi, 276000, China.
authors.forename: Shuoxin
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Second Department of Medical Oncology, Linyi Tumor Hospital, Linyi, 276000, China.
authors.forename: Guimin
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University and Nanjing Multi-Center Biobank, Nanjing, 210008, China.
authors.forename: Zhicong
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University and Nanjing Multi-Center Biobank, Nanjing, 210008, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China. wangtao_pumc@live.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China. chenwang@nju.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China. jfzhang@nju.edu.cn.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for Micro, RNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China. xichen@nju.edu.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000072283:A549 Cells; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C549214:MIRN19A microRNA, human; C474762:MTUS1 protein, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins
keywords: MTUS1; lung cancer; miR-19a/b; microRNA; migration; proliferation