SNHG15 Mediates MTSS1 Gene Expression via Interacting with the Gene Promoter and Regulating Transcription Pausing.

Int J Mol Sci

Key Immunopathology Laboratory of Guangdong Province, Department of Pathophysiology, Shantou University Medical College, Shantou 515041, China.

Published: October 2024


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Article Abstract

Metastasis suppressor 1 (MTSS1) has been reported to play important roles in suppressing cancer progression. In this study, we investigated the underlying mechanism that regulates MTSS1 expression. We showed that in breast cancer cells, lncRNA-SNHG15-induced cell invasion and proliferation was accompanied with the decreased expression of MTSS1 mRNA. Further study revealed that SNHG15 mediated MTSS1 repression through blocking its promoter activity. Mechanistically, SNHG15 complexes with DDX5 and RTF1 and interacts with the core promoter of the MTSS1 gene to interfere with RNA-Pol-II-directed transcriptional initiation. Association with DDX5 stabilizes SNHG15 while binding to RTF1 allows SNHG15 to carry RTF1 to the core promoter, where RTF1 forms a complex with PNA pl II to enhance transcriptional pausing. Our findings revealed a molecular mechanism by which SNHG15 serves as a regulator to suppresses MTSS1 transcription via interaction with the gene core promoter.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546481PMC
http://dx.doi.org/10.3390/ijms252111565DOI Listing

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