1. Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer
- Author
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Yesol Kim, Je Yeong Ko, Soo-Been Lee, Sumin Oh, Jee Won Park, Hyeok-Gu Kang, Da-Hyun Kim, Daeun Chung, Sera Lim, Hyunkyung Kong, Jongmin Kim, Kyung Hyun Yoo, Wonshik Han, Kyung-Hee Chun, and Jong Hoon Park
- Subjects
rac1 GTP-Binding Protein ,Cancer Research ,RNA-Binding Proteins ,Triple Negative Breast Neoplasms ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cell Movement ,Cell Line, Tumor ,Genetics ,Humans ,Neoplasm Invasiveness ,Molecular Biology ,Cell Proliferation - Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer; however, specific prognostic biomarkers have not yet been developed. In this study, we identified dysregulated microRNAs (miRNAs) in TNBC by profiling miRNA and mRNA expression. In patients with TNBC, miR-371b-5p expression was reduced, and miR-371b-5p overexpression significantly mitigated TNBC cell growth, migration, and invasion. In addition, we found that expression of cold shock domain-containing protein E1 (CSDE1), a direct target gene of miR-371b-5p, was upregulated in TNBC cells, and inhibition of CSDE1 expression alleviated TNBC cell growth by regulating RAC1 transcription. Mechanistically, CSDE1, phosphorylated C-terminal domain (p-CTD) of RNA polymerase II (RNAPII), and CDK7 form a complex, and downregulation of CSDE1 leads to weak interaction between RNAPII p-CTD and CDK7, resulting in a decrease in RNAPII p-CTD expression to reduce RAC1 transcript levels in CSDE1-deficient TNBC cells. Our data demonstrate that miR-371b-5p is a tumor-suppressive miRNA that regulates the CSDE1/Rac1 axis and could be a potential prognostic biomarker for TNBC.
- Published
- 2022
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