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Biochem Biophys Res Commun. 2017 Oct 21;492(3):480-486. doi: 10.1016/j.bbrc.2017.08.070. Epub 2017 Aug 20.

Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.

Author information

1
Department of Neurology, First Affiliated Hospital of Zhengzhou University, China.
2
Department of Neurosurgery, First Affiliated Hospital of Zhengzhou University, China.
3
Department of Neurology, Luoyang Central Hospital, China.
4
Department of Neurology, Zhengzhou Central Hospital, China.
5
Department of Neurology, First Affiliated Hospital of Zhengzhou University, China. Electronic address: zbadoctor@163.com.

Abstract

The long noncoding RNA Malat1 has been reported to be an oncogene that promotes tumor progress and correlates with prognosis in glioma. Growing evidence shows that autophagy plays a very important role in tumorigenesis and tumor cell survival, but whether Malat1 regulates autophagy in glioma is still unclear. In this study, we found that Malat1 expression and autophagy activity were significantly increased in glioma tissues compared with adjacent normal tissues. Additionally, Malat1 level was positively correlated with the expression of LC3-II (autophagy marker) mRNA in vivo. In vitro assays revealed that Malat1 significantly promoted autophagy activation and cell proliferation in glioma cells. More importantly, inhibition of autophagy by 3-MA relieved Malat1-induced cell proliferation. These data demonstrated that Malat1 activates autophagy and increases cell proliferation in glioma. We further investigated the molecular mechanisms whereby Malat1 functioned on glioma cell autophagy and proliferation. We found that Malat1 served as an endogenous sponge to reduce miR-101 expression by directly binding to miR-101. Moreover, Malat1 abolished the suppression effects of miR-101 on glioma cell autophagy and proliferation, which involved in upregulating the expression of miR-101 targets STMN1, RAB5A and ATG4D. Overall, our study elucidated a novel Malat1-miR-101-STMN1/RAB5A/ATG4D regulatory network that Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma cells.

KEYWORDS:

Autophagy; Glioma; Proliferation; The long noncoding RNA Malat1; miR-101

PMID:
28834690
DOI:
10.1016/j.bbrc.2017.08.070
[Indexed for MEDLINE]

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