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Biochem Biophys Res Commun. 2017 Sep 2;490(4):1260-1267. doi: 10.1016/j.bbrc.2017.05.179. Epub 2017 Jun 7.

miR-141-3p functions as a tumor suppressor modulating activating transcription factor 5 in glioma.

Author information

1
Department of Microbiology, College of Life Sciences, Qingdao University Shandong 266071, PR China.
2
Department of Basic Medical Sciences, Qingdao University, Shandong 266071, China.
3
Department of Basic Medical Sciences, Qingdao University, Shandong 266071, China. Electronic address: qiandongmeng@sina.com.
4
Department of Basic Medical Sciences, Qingdao University, Shandong 266071, China. Electronic address: wangbinmedical@163.com.
5
Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Riverpoint Blvd Spokane, WA 992082, USA.

Abstract

Glioma is the most common malignant primary brain tumor which arises from the central nervous system. Our studies reported that an anti-apoptotic factor, activating transcription factor 5 (ATF5), is highly expressed in malignant glioma specimens and cell lines. Downregulation by dominant-negetive ATF5 could repress glioma cell proliferation and accelerate apoptosis. Here, we further investigate the upstream factor which regulates ATF5 expression. Bioinformatic analysis showed that ATF5 was a potential target of miR-141-3p. Luciferase reporter assay verified that miR-141-3p specifically targeted the ATF5 3'-UTR in glioma cells. Functional studied suggested that miR-141-3p overexpression inhibited proliferation and promoted apoptosis of glioma cells (U87MG and U251). Xenograft experiments proved the inhibition of miR-141-3p on glioma growth in vivo. Moreover, exogenous ATF5 without 3'-UTR restored the cell proliferation inhibition triggered by miR-141-3p. Taken together, we put forward that miR-141-3p is a new upstream target towards ATF5. It can serve as a crucial tumor suppressor in regulating the ATF5-regulated growth of malignant glioma.

KEYWORDS:

Activating transcription factor 5; Apoptosis; Cell proliferation; Glioma; miR-141-3p

PMID:
28595907
PMCID:
PMC5759330
DOI:
10.1016/j.bbrc.2017.05.179
[Indexed for MEDLINE]
Free PMC Article

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