Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast canceropen access
- Authors
- Kim, Yesol; Ko, Je Yeong; Lee, Soo-Been; Oh, Sumin; Park, Jee Won; Kang, Hyeok-Gu; Kim, Da-Hyun; Chung, Daeun; Lim, Sera; Kong, Hyunkyung; Kim, Jongmin; Yoo, Kyung Hyun; Han, Wonshik; Chun, Kyung-Hee; Park, Jong Hoon
- Issue Date
- May-2022
- Publisher
- SPRINGERNATURE
- Citation
- ONCOGENE, v.41, no.22, pp 3151 - 3161
- Pages
- 11
- Journal Title
- ONCOGENE
- Volume
- 41
- Number
- 22
- Start Page
- 3151
- End Page
- 3161
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/152777
- DOI
- 10.1038/s41388-022-02326-6
- ISSN
- 0950-9232
1476-5594
- 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.
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