Down-Regulating the Expression of miRNA-21 Inhibits the Glucose Metabolism of A549/DDP Cells and Promotes Cell Death Through the PI3K/AKT/mTOR/HIF-1α Pathway

被引:27
作者
Sun, Ye [1 ,2 ]
Liu, Wenjun [3 ]
Zhao, Qiuyu [4 ]
Zhang, Ruiqi [5 ]
Wang, Jianbo [4 ]
Pan, Pengyu [1 ]
Shang, Hai [6 ]
Liu, Chunying [1 ]
Wang, Chun [1 ]
机构
[1] Liaoning Univ Tradit Chinese Med, Dept Cell Biol, Coll Integrated Chinese & Western Med, Shenyang, Peoples R China
[2] Shenyang Med Coll, Key Lab Environm Pollut & Microecol Liaoning Prov, Shenyang, Peoples R China
[3] Liaoning Univ Tradit Chinese Med, Teaching & Expt Ctr, Shenyang, Peoples R China
[4] Liaoning Univ Tradit Chinese Med, Key Lab, Minist Educ Tradit Chinese Med TCM Viscera State, Shenyang, Peoples R China
[5] Northeast Yucai Sch, Shenyang, Peoples R China
[6] China Med Univ, Liaoning Canc Hosp & Inst, Canc Hosp, Shenyang, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2021年 / 11卷
关键词
non-small cell lung cancer; cisplatin resistance; miRNA-21; PI3K; AKT; mTOR; glycolysis; CANCER;
D O I
10.3389/fonc.2021.653596
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
miRNA-21 is a single-stranded non-coding RNA that is highly expressed in a variety of tumor cells. It participates in tumor cell proliferation, metabolism, metastasis, and drug resistance. Here, we tested the potential mechanism of miRNA-21 in cisplatin-resistant non-small cell lung cancer A549/DDP (human lung adenocarcinoma drug-resistant cell line) cells. A549 and A549/DDP RNAs were sequenced to show that miRNA-21 was highly expressed in the latter, and this was verified by qRT-PCR. In addition, we found that miRNA-21 combined with cisplatin can significantly inhibit glycolysis and glycolysis rate-limiting enzyme protein expression in A549/DDP cells. We also found that miRNA-21 combined with cisplatin can promote A549/DDP cell death. Further investigations showed that miRNA-21 combined with cisplatin caused excessive inactivation of the pI3K/AKT/mTOR/HIF-1 alpha signaling pathway in cisplatin-resistant A549/DDP cells. Hence, reduction of the expression of miRNA-21 in combination with cisplatin chemotherapy may effectively improve the therapeutic effect on patients with non-small cell lung cancer, and this may provide a theoretical basis for the treatment of this disease.
引用
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页数:11
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