Overexpression of secretagogin inhibits cell apoptosis and induces chemoresistance in small cell lung cancer under the regulation of miR-494

被引:50
作者
Bai, Yifeng [1 ,2 ,3 ]
Sun, Yanqin [1 ,4 ]
Peng, Juan [1 ,5 ]
Liao, Hongzhan [6 ]
Gao, Hongyi [1 ,7 ]
Guo, Ying [8 ]
Guo, Linlang [1 ]
机构
[1] Southern Med Univ, Zhujiang Hosp, Dept Pathol, Guangzhou, Guangdong, Peoples R China
[2] Sichuan Acad Med Sci, Dept Oncol, Chengdu, Peoples R China
[3] Sichuan Prov Peoples Hosp, Chengdu, Peoples R China
[4] Guangdong Med Coll, Sch Basic Med Sci, Dept Pathol, Dongguan, Peoples R China
[5] Guangzhou Med Univ, Affiliated Hosp 3, Dept Pathol, Guangzhou, Guangdong, Peoples R China
[6] Southern Med Univ, Zhujiang Hosp, Dept Neurosurg, Guangzhou, Guangdong, Peoples R China
[7] Guangdong Women & Children Hosp, Dept Pathol, Guangzhou, Guangdong, Peoples R China
[8] Southern Med Univ, Zhujiang Hosp, Dept Organ Transplantat, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
SCGN; miR-494; SCLC; chemoresistance; DOWN-REGULATION; CA2+-BINDING PROTEIN; EXPRESSION; MICRORNA; RESISTANCE; CISPLATIN; TARGETS; PTEN; DIFFERENTIATION; PROLIFERATION;
D O I
10.18632/oncotarget.2305
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Secretagogin (SCGN) has recently been identified to play a crucial role in cell apoptosis, receptor signaling and differentiation. However, its clinical significance and functional roles in SCLC chemoresistance remain unknown. Here we examined the expression of SCGN in clinical samples from SCLC patients and evaluated its relation with clinical prognosis. Then up and down-regulation of SCGN were carried out in SCLC cell lines to assess its influence on chemoresistance. Furthermore, luciferase reporter assay was used to evaluate whether SCGN is a novel direct target of miR-494. Our results revealed that elevated expression of SCGN was correlated with the poorer prognosis of SCLC patients and the more significant correlation with chemosensitivity. We also found that knockdown of SCGN expression in H69AR and H446AR cells increased chemosensitivity via increasing cell apoptosis and cell cycle arrest of G0/G1 phase, while over-expression of SCGN reduced chemosensitivity in sensitive H69 and H446 cells. SCGN as a novel target of miR-494 by luciferase reporter assay, up-regulation of miR-494 can sensitize H69AR cells to chemotherapeutic drugs. These results suggest SCGN is involved in the chemoresistance of SCLC under the regulation of miR-494 and may be a potential biomarker for predicting therapeutic response in treatment SCLC.
引用
收藏
页码:7760 / 7775
页数:16
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