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Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer. | LitMetric

AI Article Synopsis

  • Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer lacking specific prognostic biomarkers, prompting research into microRNAs (miRNAs) influencing its characteristics.
  • The study revealed that the expression of miR-371b-5p is decreased in TNBC, and increasing its levels can significantly reduce tumor growth, migration, and invasion.
  • Additionally, miR-371b-5p directly targets the CSDE1 gene, and its downregulation affects the RAC1 signaling pathway, suggesting that miR-371b-5p could serve as a potential prognostic biomarker for TNBC treatment and management.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135623PMC
http://dx.doi.org/10.1038/s41388-022-02326-6DOI Listing

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