MicroRNA-222 alleviates radiation-induced apoptosis by targeting BCL2L11 in cochlea hair cells

被引:1
作者
Zhang, Yan-yan [1 ]
Xiong, Gao-yun [1 ]
Xie, Xiao-xing [1 ]
机构
[1] Tongde Hosp Zhejiang Prov, Dept Otolaryngol, Hangzhou 310012, Peoples R China
关键词
CANCER; OTOTOXICITY; MECHANISMS;
D O I
10.1042/BSR20201397
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Radiation-induced hair cell injury is detrimental for human health but the underlying mechanism is not clear. MicroRNAs (miRNAs) have critical roles in various types of cellular biological processes. The present study investigated the role of miR-222 in the regulation of ionizing radiation (IR)-induced cell injury in auditory cells and its underlying mechanism. Real-time PCR was performed to identify the expression profile of miR-222 in the cochlea hair cell line HEI-OC1 after IR exposure. miRNA mimics or inhibitor-mediated up- or down-regulation of indicated miRNA was applied to characterize the biological effects of miR-222 using MTT, apoptosis and DNA damage assay. Bioinformatics analyses and luciferase reporter assays were applied to identify an miRNA target gene. Our study confirmed that IR treatment significantly suppressed miR-222 levels in a dose-dependent manner. Up-regulation of miR-222 enhances cell viability and alleviated IR-induced apoptosis and DNA damage in HEI-OC1 cells. In addition, BCL-2-like protein 11 (BCL2L11) was validated as a direct target of miR-222. Overexpression of BCL2L11 abolished the protective effects of miR-222 in IR-treated HEI-OC1 cells. Moreover, miR-222 alleviated IR-induced apoptosis and DNA damage by directly targeting BCL2L11. The present study demonstrates that miR-222 exhibits protective effects against irradiation-induced cell injury by directly targeting BCL2L11 in cochlear cells.
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页数:10
相关论文
共 19 条
[1]   BCL2L11/Bim as a dual-agent regulating autophagy and apoptosis in drug resistance [J].
Dai, Yun ;
Grant, Steven .
AUTOPHAGY, 2015, 11 (02) :416-418
[2]   MiR-222 in Cardiovascular Diseases: Physiology and Pathology [J].
Ding, Shengguang ;
Huang, Haitao ;
Xu, Yiming ;
Zhu, Hao ;
Zhong, Chongjun .
BIOMED RESEARCH INTERNATIONAL, 2017, 2017
[3]   The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics [J].
Hata, Aaron N. ;
Engelman, Jeffrey A. ;
Faber, Anthony C. .
CANCER DISCOVERY, 2015, 5 (05) :475-487
[4]   Involvement of miR-155/FOXO3a and miR-222/PTEN in acquired radioresistance of colorectal cancer cell line [J].
Khoshinani, Hamed Manoochehri ;
Afshar, Saeid ;
Pashaki, Abdolazim Sedighi ;
Mahdavinezhad, Ali ;
Nikzad, Safora ;
Najafi, Rezvan ;
Amini, Razieh ;
Gholami, Mohammad Hadi ;
Khoshghadam, Alireza ;
Saidijam, Massoud .
JAPANESE JOURNAL OF RADIOLOGY, 2017, 35 (11) :664-672
[5]   Cellular mechanisms of noise-induced hearing loss [J].
Kurabi, Arwa ;
Keithley, Elizabeth M. ;
Housley, Gary D. ;
Ryan, Allen F. ;
Wong, Ann C. -Y. .
HEARING RESEARCH, 2017, 349 :129-137
[6]   Ototoxicity and Cancer Therapy [J].
Landier, Wendy .
CANCER, 2016, 122 (11) :1647-1658
[7]   MicroRNAs: effective elements in ear-related diseases and hearing loss [J].
Mahmoudian-sani, Mohammad-Reza ;
Mehri-Ghahfarrokhi, Ameneh ;
Ahmadinejad, Fereshteh ;
Hashemzadeh-Chaleshtori, Morteza ;
Saidijam, Massoud ;
Jami, Mohammad-Saeid .
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY, 2017, 274 (06) :2373-2380
[8]   Role of microRNAs in inner ear development and hearing loss [J].
Mittal, Rahul ;
Liu, George ;
Polineni, Sai P. ;
Bencie, Nicole ;
Yan, Denise ;
Liu, Xue Zhong .
GENE, 2019, 686 :49-55
[9]   MicroRNA therapeutics: towards a new era for the management of cancer and other diseases [J].
Rupaimoole, Rajesha ;
Slack, Frank J. .
NATURE REVIEWS DRUG DISCOVERY, 2017, 16 (03) :203-221
[10]  
Shi LQ, 2019, INT J CLIN EXP PATHO, V12, P4204