The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1852

Article

Deng, Hui¹  Lv, Lei¹  Li, Yang²  Zhang, Cheng³  Meng, Fang⁴  Pu, Youguang¹  Xiao, Jun^1,5  Qian, Liting⁴  Zhao, Weidong⁶  Liu, Qi⁷  Zhang, Daming⁸  Wang, Yingwei⁹  Zhang, Hongyu¹⁰  He, Yinghua¹⁰  Zhu, Jingde^1,10 

[1] Anhui Canc Hosp, Canc Epigenet Program, Hefei 230031, Anhui, Peoples R China

[2] Anhui Med Univ, Sch Life Sci, Dept Biol, Hefei 230031, Anhui, Peoples R China

[3] Harbin Med Univ, Affiliated Hosp 1, Dept Urol, Harbin, Heilongjiang Pr, Peoples R China

[4] Anhui Canc Hosp, Dept Radiotherapy, Hefei 230031, Anhui, Peoples R China

[5] Anhui Prov Hosp, Dept Urol, Hefei, Peoples R China

[6] Anhui Canc Hosp, Dept Gynecol Canc, Hefei 230031, Anhui, Peoples R China

[7] Harbin Inst Technol, State Key Lab Urban Water Resource & Environm, Sch Life Sci & Technol, Harbin 150001, Heilongjiang, Peoples R China

[8] Harbin Med Univ, Affiliated Hosp 1, Dept Neurosurg, Harbin, Heilongjiang Pr, Peoples R China

[9] Harbin Med Univ, Affiliated Hosp 1, Dept Pathol, Harbin, Heilongjiang Pr, Peoples R China

[10] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, Canc Epigenet Program, Shanghai 200032, Peoples R China

关键词: PSEN1;    miR-193a-3p;    Chemoresistance;    Bladder cancer;    DNA damage response pathway;   

DOI  :  10.1016/j.bbadis.2014.12.014

来源: Elsevier

【 摘 要 】

Chemoresistance prevents the curative cancer therapy, our understanding of which remains inadequate. Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer. (C) 2014 Elsevier B.V. All rights reserved.

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