miR-1205/DNAJB1 reverses docetaxel chemoresistance in human triple negative breast carcinoma cells via regulation of mutp53/TAp63 signaling  

作　　者：Yongxiang Yin Jinqiu Zhang Tao Ma Daozhen Chen Daru Lu 

机构地区：[1]Department of Pathology,The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University,Wuxi 214002,China [2]State Key Laboratory of Genetic Engineering and MOE Engineering Research Center of Gene Technology,School of Life Sciences,Fudan University,Shanghai 200438,China [3]Central Laboratory,The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University,Wuxi 214002,China [4]Department of Breast,The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University,Wuxi 214002,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第1期37-46,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from Wuxi“Taihu Talent”Research Project(No.BJ2020072);Project of Wuxi Municipal Health Bureau(No.MS201947).

摘　　要：Chemoresistance is the major cause of therapeutic failure in human triple negative breast carcinoma(TNBC).Docetaxel(DOC),a first-line therapeutic drug in TNBC treatment,is limited for long-term use due to the development of chemoresistance.Thus,overcoming chemoresistance of DOC remains an important challenge to improve patient’s outcome of TNBC.In this study,we aimed to investigate the molecular mechanism behind DOC chemoresistance and the possible therapeutic effects of miRNAs.Utilizing qRT-PCR analysis,we discovered that miR-1205 is gradually downregulated in human triple negative breast carcinoma MDA-MB-231 and docetaxel-resistant MDA-MB-231(MDA-MB-231/DOC)cells compared with Hs 578Bst normal human breast fibroblasts.Cell viability,cell cycle and apoptosis assays in MDA-MB-231/DOC cells indicated that miR-1205 overexpression enhances docetaxel sensitivity by reducing cell viability as well as inducing G2/M cell cycle arrest and cell apoptosis.Western blot analysis,dual-luciferase reporter assay,co-immunoprecipitation assay and chromatin immunoprecipitation assay revealed that miR-1205 overexpression disrupts the stable complex formation of DNAJB1,mutp53 and TAp63 by directly reducing DNAJB1 expression,which abates the sequestrating effect of mutp53 on TAp63,thereby leading to the enhanced DOC sensitivity in MDA-MB-231/DOC cells.Our findings demonstrate the role of the miR-1205/DNAJB1 axis in the docetaxel resistance of TNBC,which may offer a promising therapeutic approach to resolve docetaxel resistance in TNBC.

关 键 词：triple negative breast carcinoma docetaxel resistance miR-1205/DNAJB1 mutp53/TAp63 signaling 

分 类 号：R737.9[医药卫生—肿瘤]