title: miR-28-5p acts as a tumor suppressor in renal cell carcinoma for multiple antitumor effects by targeting RAP1B.
abstract: The incidence and mortality rate of renal cell carcinoma (RCC) have been significantly increasing; however, the mechanisms involved in RCC development and progression are unclear. In this study, we found that miR-28-5p was decreased in RCC tumor specimens and several renal carcinoma cell lines. By using a combination of luciferase reporter assays and western blotting, we identified RAP1B, a Ras-related small GTP-binding oncoprotein implicated in a variety of tumors, as a direct target of miR-28-5p in RCC. The RAP1B protein level was increased in RCC tumor specimens and renal carcinoma cell lines, and this was inversely correlated with miR-28-5p expression. In vitro gain-of-function and loss-of-function studies in human renal carcinoma cell lines, demonstrated that miR-28-5p suppressed cell proliferation and migration by directly inhibiting RAP1B, and this effect was reversed by co-transfection with RAP1B. In addition, the stable overexpression of miR-28-5p inhibited tumor cell proliferation in vivo. This newly identified miR-28-5p/RAP1B axis provides a novel mechanism for the pathogenesis of RCC, and molecules in this axis may serve as potential biomarkers and therapeutic targets for RCC.
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210002, China.|State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210023, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210002, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210002, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210002, China.|State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210023, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210002, China.
authors.forename: Jinsha
authors.initials: J
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210023, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Department of Urology, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing 210002, China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210002, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Jinling Hospital, State Key Laboratory of Analytical Chemistry for Life Science, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210002, China.|State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing 210023, China.
authors.forename: Chunni
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation; D034622:RNA Interference; D020668:rap GTP-Binding Proteins / Q000235:genetics*
chemical_list: C570628:MIRN28 microRNA, human; D035683:MicroRNAs; C116753:RAP1B protein, human; D020668:rap GTP-Binding Proteins
keywords: RAP1B; miR-28-5p; migration; proliferation; renal cell carcinoma