MiR-34c acts as a tumor suppressor in non-small cell lung cancer by inducing endoplasmic reticulum stress through targeting HMGB1

被引：26

作者：

Tu, Li ^{[1
,2
]}

Long, Xiang ^{[2
]}

Song, Weidong ^{[2
]}

Lv, Zhongdong ^{[2
]}

Zeng, Huadong ^{[1
]}

Wang, Tiezhu ^{[3
]}

Liu, Xianglu ^{[2
]}

Dong, Juanni ^{[2
]}

Xu, Ping ^{[2
]}

机构：

[1] Southern Med Univ, Shenzhen Hosp, Dept Resp Med, Shenzhen 518000, Peoples R China

[2] Peking Univ, Dept Resp Med, Shenzhen Hosp, 1120 Lianhua Rd Futian Area, Shenzhen 518000, Peoples R China

[3] Zhangzhou Municipal Hosp Fujian Prov, Dept Resp Med, Zhangzhou 363000, Peoples R China

来源：

ONCOTARGETS AND THERAPY | 2019年 / 12卷

关键词：

non-small cell lung cancer; microRNA; high mobility group box 1; endoplasmic reticulum stress; ER stress; ER STRESS; APOPTOSIS; AXIS; ROS;

D O I：

10.2147/OTT.S206932

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Objective: To investigate the role of miR-34c in lung cancer. Methods: The levels of microRNA-34c (miR-34c) expression in non-small cell lung cancer (NSCLC) tissue and cell lines were examined by the qRT-PCR assay. High mobility group box 1 (HMGB1) expression in NSCLC was assessed by immunohistochemical analysis (IHC), qRT-PCR, and Western blot assays. The effects of miR-34c overexpression or HMGB1 knockdown on cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry analysis, respectively. Cellular reactive oxygen species (ROS) production in NSCLC cells was detected using a ROS kit. The levels of Bax, p-ERK, eIF2 alpha, GADD153, and IRE1 alpha expression in treated NSCLC cells were measured by Western blot assays. In addition, the interaction between miR-34c and HMGB1 was verified by the dual-luciferase reporter assay. Results: miR-34c was only slightly expressed, while HMGB1 was highly expressed in NSCLC tissues and cell lines. Overexpression of miR-34c or knockdown of HMGB1 inhibited cell proliferation, promoted cell apoptosis, and induced ER stress in NSCLC cells. In terms of mechanism, miR-34c negatively regulated HMGB1 expression by directly targeting the 3'-untranslated region (UTR) of HMGB1 mRNA. In addition, we proved that HMGB1 overexpression could block the effects of miR-34c on NSCLC cell proliferation, apoptosis, and ER stress. Conclusion: miR-34c may suppress NSCLC tumors by targeting HMGB1 mRNA, promoting endoplasmic reticulum stress, and increasing ROS levels. Our findings suggest that miR34c has a role in NSCLC.

引用

页码：5729 / 5739

页数：11