Oncotarget

Research Papers:

MicroRNA16 regulates glioma cell proliferation, apoptosis and invasion by targeting Wip1-ATM-p53 feedback loop

Xiao-Hong Zhan, Qiu-Yan Xu, Rui Tian, Hong Yan, Min Zhang, Jing Wu, Wei Wang and Jie He _

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Oncotarget. 2017; 8:54788-54798. https://doi.org/10.18632/oncotarget.18510

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Abstract

Xiao-Hong Zhan1,2,3,*, Qiu-Yan Xu2,*, Rui Tian2, Hong Yan2, Min Zhang2, Jing Wu2, Wei Wang4 and Jie He1,2

1School of Medicine, Shandong University, Jinan 250012, Shangdong Province, P.R. China

2Department of Pathology, Anhui Provincial Cancer Hospital; Anhui Provincial Hospital, Anhui Medical University, Hefei 230031, Anhui Province, P.R. China

3Department of Pathology, The Affiliated Central Hospital of Qingdao University, Qingdao 266000, Shandong Province, P.R. China

4Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, Anhui Province, P.R. China

*These authors contributed equally as co-first author

Correspondence to:

Jie He, email: [email protected]

Wei Wang, email: [email protected]

Keywords: glioma, microRNA16, Wip1, ATM, p53

Received: December 08, 2016     Accepted: May 27, 2017     Published: June 16, 2017

ABSTRACT

The present study aimed to investigate the role and underlying mechanisms of microRNA16 (miR-16) on proliferation, apoptosis and invasion of glioma cells. The cell models of miR-16 upregulation and Negative control group (NC group) were built. The cell functions of different groups were detected by colony formation assay, transwell chamber assay, proliferation, apoptosis and cycle experiments. The intracranial orthotopic transplantation animal models were built to different groups: miR-16 agomir group, miR-16 antagomir group and their NC group. The expressions of miR-16, Wip1, ATM and p53 were measured by qRT-PCR, western blot and immunohistochemistry. As a result, miR-16 overexpressed groups had lower cloning formation rate and proliferation rate, less invasive cells, higher early apoptosis rate than the control groups. G1 phase was significantly smaller compared miR-16 overexpressed groups with the control groups, and S phase significantly lesser. Cell growth was retardated. Differences were statistically significant (P <0.05). Compared with miR-16 overexpressed groups and NC groups, the Wip1 gene and protein expression were downregulated, while ATM and p53 genes, p-ATM and p-p53 proteins were upregulated. The differences were statistically significant (P <0.05). Taken together, our findings demonstrated that miR-16 suppressed glioma cell proliferation and invasion, promoted apoptosis and inhibited cell cycle by targeting Wip1-ATM-p53 signaling pathway.


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