miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells

被引：37

作者：

Mao, Aihong ^{[1
,2
,3
,6
]}

Liu, Yang ^{[1
,4
,5
]}

Wang, Yali ^{[1
,4
,5
]}

Zhao, Qiuyue ^{[1
,4
,5
,6
]}

Zhou, Xin ^{[1
,4
,5
]}

Sun, Chao ^{[1
,4
,5
]}

Di, Cuixia ^{[1
,4
,5
]}

Si, Jing ^{[1
,4
,5
]}

Gan, Lu ^{[1
,4
,5
]}

Zhang, Hong ^{[1
,4
,5
,7
]}

机构：

[1] Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Peoples R China

[2] Lanzhou Univ, Sch Nucl Sci & Technol, Lanzhou 730000, Peoples R China

[3] Inst Gansu Med Sci Res, Lanzhou 730050, Peoples R China

[4] Chinese Acad Sci, Key Lab Heavy Ion Radiat Med, Lanzhou 730000, Peoples R China

[5] Key Lab Heavy Ion Radiat Med Gansu Prov, Lanzhou 730000, Peoples R China

[6] Univ Chinese Acad Sci, Beijing 100039, Peoples R China

[7] Chinese Acad Sci, Inst Modern Phys, Dept Heavy Ion Radiat Med, 509 Nanchang Rd, Lanzhou 730000, Peoples R China

来源：

TUMOR BIOLOGY | 2016年 / 37卷 / 04期

基金：

中国国家自然科学基金;

关键词：

miR-449a; G2/Marrest; Apoptosis; pRb/E2F1; Radiosensitivity; Prostate cancer; CYCLE; TARGETS; ARREST; PROLIFERATION; MECHANISMS; EXPRESSION; MICRORNAS; APOPTOSIS; GROWTH;

D O I：

10.1007/s13277-015-4336-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

miR-449a, a novel tumor suppressor, is deregulated in various malignancies, including prostate cancer. Overexpression of miR-449a induces cell cycle arrest, apoptosis, and senescence, but its role in response to ionizing radiation and underlying molecular mechanism are still unknown. Here, we report that miR-449a enhances radiation-induced G2/M phase arrest and apoptosis through modulating pRb/E2F1 and sensitizes prostate cancer cells to X-ray radiation. In wild-type Rb PC-3 cells, overexpression of miR-449a enhances radiation-induced G2/M arrest and apoptosis and promotes the sensitivity to X-ray radiation. While mutant Rb DU-145 cells are resistant to the X-ray radiation despite in the presence of miR-449a. The cell cycle distribution of DU-145 cells is not significantly altered by miR-449a in the response to ionizing radiation. Furthermore, elevated miR-449a downregulates cell cycle regulator CDC25A and oncogene HDAC1. By targeting genes involved in controlling pRb/E2F1 activity, miR-449a regulates cell cycle progression and apoptosis and consequently enhances the radiosensitivity of PC-3 cells. Thus, miR-449a, as a miRNA component of the Rb pathway, promotes the radiosensitivity of PC-3 cells through regulating pRb/E2F1.

引用

页码：4831 / 4840

页数：10

共 45 条

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