title: Oncogenic cAMP responsive element binding protein 1 is overexpressed upon loss of tumor suppressive miR-10b-5p and miR-363-3p in renal cancer.
abstract: Renal cell carcinoma (RCC) is the most common kidney cancer in adults and has a poor prognosis. cAMP responsive element binding protein 1 (CREB1) is a proto‑oncogenic transcription factor involved in malignancies of various organs. However, its functional role(s) have not yet been elucidated in RCC. We investigated the expression pattern, function and regulation of CREB1 in RCC. CREB1 was overexpressed in the RCC tissues and cell lines. Downregulation of CREB1 inhibited RCC tumorigenesis by affecting cell proliferation, migration and apoptosis. Multiple computational algorithms predicted that the 3'‑untranslated region (3'‑UTR) of human CREB1 mRNA is a target for miR‑10b‑5p and miR‑363‑3p. Luciferase reporter assay, qPCR and western blot analysis confirmed that miR‑10b‑5p and miR‑363‑3p bind directly to the 3'‑UTR of CREB1 mRNA and inhibit mRNA and protein expression of CREB1. qPCR data also revealed a significantly lower expression of miR‑10b‑5p and miR‑363‑3p in RCC tissues. Introduction of miR‑10b‑5p and miR‑363‑3p mimics led to suppressed expression of CREB1 and inhibited cell proliferation, migration and apoptosis reduction. Taken together, we propose that CREB1 is an oncogene in RCC and that upregulation of CREB1 by loss of tumor suppressive miR‑10b‑5p and miR‑363‑3p plays an important role in the tumorigenesis of RCC.
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Duqun
authors.initials: D
authors.lastname: Chen
authors.affiliation: The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Yuchi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Jiaju
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Su
authors.affiliation: The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Qi
authors.affiliation: The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Zhimao
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Liangchao
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Shangqi
authors.initials: S
authors.lastname: Yang
authors.affiliation: The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Ultrasound Division, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Urology, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C547183:MIRN10 microRNA, human; C574861:MIRN363 microRNA, human; D035683:MicroRNAs