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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wang X,Liang Z,Xu X,Li J,Zhu Y,Meng S,Li S,Wang S,Xie B,Ji A,Liu B,Zheng X,Xie L

doi

10.1038/cddis.2016.373

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

e2503

issue

12

issn

2041-4889

pii

cddis2016373

journal_volume

7

pub_type

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