Oncotarget

Research Papers:

MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by directly targeting p53

Xu Zhou, Weining Wu, Ailiang Zeng, Er Nie, Xin Jin, Tianfu Yu, Tongle Zhi, Kuan Jiang, Yingyi Wang, Junxia Zhang and Yongping You _

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Oncotarget. 2017; 8:71080-71094. https://doi.org/10.18632/oncotarget.20528

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Abstract

Xu Zhou1,*, Weining Wu1,*, Ailiang Zeng1, Er Nie1, Xin Jin1, Tianfu Yu1, Tongle Zhi1, Kuan Jiang1, Yingyi Wang1, Junxia Zhang1 and Yongping You1

1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China

*These authors have contributed equally to this work

Correspondence to:

Yongping You, email: [email protected]

Keywords: glioblastoma, proliferation, TMZ resistance, microRNA, p53

Abbreviations: GBM, glioblastoma multiforme; miRNAs, microRNAs; TMZ, temozolomide; CCK-8, Cell Counting Kit-8; EdU, 5-ethynyl-2′-deoxyuridine

Received: February 18, 2017     Accepted: July 29, 2017     Published: August 24, 2017

ABSTRACT

Glioblastoma multiforme is the most common primary malignancy in the brain and confers a uniformly poor prognosis. MicroRNAs have been shown to activate or inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in various cancers and correlate with tumor formation. We examined the expression of microRNA-141-3p (miR-141-3p) in glioma of different grades by analysis of expression profiling databases and clinical specimens. Cell proliferation and flow cytometry assays were performed to evaluate the promotion of miR-141-3p in proliferation, cell cycle, apoptosis, and temozolomide resistance of glioblastoma cells in vitro. Bioinformatics analyses, luciferase reporter assays, and immunoblotting showed that p53 is a target gene of miR-141-3p. A significant inverse correlation was observed between expression of miR-141-3p and p53 in glioma and normal brain tissues (R2=0.506, P<0.0001). Rescue experiments indicated that overexpression of p53 significantly reversed the alterations in proliferation, cell cycle distribution, and temozolomide resistance measured by cell apoptosis induced by miR-141-3p overexpression. In an orthotopic mouse model of human glioma, inhibition of miRNA-141-3p reduced the proliferation and growth of glioma cells in the brain and significantly prolonged the survival of glioma-bearing mice. We suggest that miR-141-3p promotes glioblastoma progression and temozolomide resistance by altering p53 expression and therefore may serve as a new diagnostic marker and therapeutic target for glioma in the future.


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