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KMID : 1034820220180010101
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Molecular & Cellular Toxicology
2022 Volume.18 No. 1 p.101 ~ p.110
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KLF5-trancripted miR-125b-5p is involved in enhancing the radio-sensitivity of breast cancer cells by targeting BRCA1
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Gong Ting
Jia Bin
Gu Liyan
Yu Tao
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Abstract
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Background: A large number of clinical trials have proved that radiotherapy is an effective strategy for treating breast cancer (BC), but radioresistance is an urgent problem to be solved.
Objective: Herein, radio-tolerant BC cell lines named MDA-MB-231/R and MCF-7/R were successfully constructed, respectively, and it was shown that microRNA-125b-5p (miR-125b-5p) was lowly expressed in radio-tolerant cells, which was associated with poor prognosis of BC patients.
Results: Furthermore, miR-125b-5p over expression could hinder cell proliferation and strengthen radio-sensitivity. Mechanistically, Breast Cancer 1 (BRCA1) was identified as a downstream protein target of miR-125b-5p in BC cells, and Kruppel-like factor 5 (KLF5) was identified as an upstream transcription factor involved in promoting miR-125b-5p expression. More importantly, over expression of KLF5 suppressed BC cell proliferation and increased its radiation sensitivity, which could be retained by miR-125b-5p downregulation.
Conclusion: In conclusion, these findings suggested that the KLF5/miR-125b-5p/BRCA1 axis may provide new information on radiation therapy for breast cancer.
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KEYWORD
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Kruppel-like factor 5, Breast cancer, miR-125b-5p, Radio-resistance, Breast cancer cells, Proliferation
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