title: miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer.
abstract: miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells. miR-148a-3p inhibits bladder cancer cell proliferation and epithelial-mesenchymal transition (EMT) by regulating ERBB3/AKT2/c-myc and ERBB3/AKT2/Snail signaling. ERBB3, DNMT1 and AKT2 are downstream miR-148a-3p target genes. Furthermore, the miR-148a-3p/ERBB3/AKT2/c-myc signaling axis establishes a positive feedback loop in the regulation of bladder cancer. Taken together, our study demonstrates novel regulatory circuits involving miR-148a-3p/ERBB3/AKT2/c-myc and DNMT1 that controls bladder cancer progression, which may be useful in the development of more effective therapies against bladder cancer.
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Meng
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Alin
authors.initials: A
authors.lastname: Ji
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Ben
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Xie
mesh_terms: D000368:Aged; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D025461:Feedback, Physiological; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D015999:Multivariate Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D004248:DNA (Cytosine-5-)-Methyltransferases; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3; D051057:Proto-Oncogene Proteins c-akt