Micro-RNA29b enhances the sensitivity of glioblastoma multiforme cells to temozolomide by promoting autophagy

被引:6
作者
Xu, Jing-Xuan [1 ]
Yang, Yan [1 ]
Zhang, Xu [1 ]
Luan, Xin-Ping [1 ]
机构
[1] XinJiang Med Univ, Affiliated Hosp 2, Dept Neurosurg, Urumqi, Peoples R China
来源
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY | 2021年 / 304卷 / 02期
关键词
autophagy; glioblastoma multiforme; microRNA29b; temozolomide; REPORT PRIMARY BRAIN; UNITED-STATES; RESISTANCE; CANCER; MANAGEMENT; APOPTOSIS; INDUCTION; MIR-29B; PROTEIN;
D O I
10.1002/ar.24400
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
To explore whether or not aberrant expression of miR-29b in glioblastoma multiforme (GBM) cells was associated with temozolomide (TMZ) resistance and to elucidate potential underlying mechanisms. Upregulation of miR-29 in GBM cells was achieved by transfecting miR-29b mimics. Changes in cell viability were measured by using CCK-8 assays. Flow cytometry and TUNEL assays were used to quantify the number of apoptotic cells. The expression levels of apoptosis-related proteins as well as autophagy-associated proteins, and the expression levels of both apoptotic and autophagic genes were determined by Western blotting. Autophagy flux was monitored by transfecting mRFP-GFP-LC3 adenovirus. We halted autophagy by introducing Atg 5-specific siRNA or the autophagy inhibitor Bafilomycin A1 (Baf-A1). We also employed a GBM xenograft mice model to confirm the role of miR-29b in vivo. miR-29b overexpression induced inhibition of cell viability, and also induced apoptosis and autophagy in U251 and U87MG cells. Furthermore, upregulation of miR-29b was able to potentiate the level of antitumor activity of TMZ against tested cells. We also found that autophagy induced by miR-29b, at least partially, contributed to the increase of TMZ sensitivity in GBM cells. As was evidenced by blockade of autophagy, the application of Atg 5 siRNA or Baf-A1 was able to significantly reverse these effects. Consistent with observations in vitro, findings of in vivo assessment also confirmed that overexpression of miR-29b was able to effectively halt tumor growth and enhance the antitumor activity of TMZ. miR-29b potentiates TMZ sensitivity against GBM cells by inducing autophagy and the combined use of miR-29 mimic and TMZ might represent a potential therapeutic strategy for GBM patients.
引用
收藏
页码:342 / 352
页数:11
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