MiR-22 suppresses epithelial-mesenchymal transition in bladder cancer by inhibiting Snail and MAPK1/Slug/vimentin feedback loop.

Abstract:

:MicroRNAs (miRNAs) have been validated to play prominent roles in the occurrence and development of bladder cancer (BCa). MiR-22 was previously reported to act as a tumor suppressor or oncomiRNA in various types of cancer. However, its accurate expression, function, and mechanism in BCa remain unclear. Here, we find that miR-22 is frequently downregulated in BCa tissues compared with adjacent non-cancerous tissues. Overexpression of miR-22 significantly inhibits proliferation, migration, and invasion of BCa cells both in vitro and in vivo. Importantly, miR-22 is found to suppress cell proliferation/apoptosis by directly targeting MAPK1 (mitogen-activated protein kinase 1, ERK2) and inhibit cell motility by targeting both MAPK1 and Snail. Further statistical analysis shows that low-expression of MAPK1 or Snail is an independent prognostic factor for a better overall survival in patients with BCa (n = 401). Importantly, we describe an important regenerative feedback loop among vimentin, Slug and MAPK1 in BCa cells. MAPK1-induced Slug expression upregulates vimentin. Vimentin in turn activates MAPK1. By inhibiting Snail and MAPK1/Slug/vimentin feedback loop, miR-22 suppresses epithelial-mesenchymal transition (EMT) of BCa cells in vitro as well as in vivo. Taken together, this study reveals that miR-22 is critical to the proliferation, apoptosis and EMT progression in BCa cells. Targeting the pathway described here may be a novel approach for inhibiting proliferation and metastasis of BCa.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Xu M,Li J,Wang X,Meng S,Shen J,Wang S,Xu X,Xie B,Liu B,Xie L

doi

10.1038/s41419-017-0206-1

subject

Has Abstract

pub_date

2018-02-12 00:00:00

pages

209

issue

2

issn

2041-4889

pii

10.1038/s41419-017-0206-1

journal_volume

9

pub_type

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