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SNHG15 Mediates MTSS1 Gene Expression via Interacting with the Gene Promoter and Regulating Transcription Pausing
Yanchun Zhou1, Shaoying Chen1, Weibin Chen1
1Key Immunopathology Laboratory of Guangdong Province, Department of Pathophysiology, Shantou University Medical College, Shantou 515041, China.
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.
Insights
Long non-coding RNA SNHG15 suppresses metastasis suppressor 1 (MTSS1) expression in breast cancer. SNHG15 complexes with proteins to block MTSS1 transcription, promoting cancer cell invasion and proliferation.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- Metastasis suppressor 1 (MTSS1) is crucial for inhibiting cancer progression.
- Understanding the regulation of MTSS1 expression is vital for developing cancer therapies.
Purpose of the Study:
- To elucidate the mechanism controlling MTSS1 gene expression.
- To investigate the role of long non-coding RNA SNHG15 in MTSS1 regulation.
Main Methods:
- Investigated SNHG15 effects on MTSS1 mRNA levels in breast cancer cells.
- Analyzed SNHG15 interaction with the MTSS1 promoter region.
- Utilized co-immunoprecipitation to identify protein complexes involving SNHG15, DDX5, and RTF1.
Main Results:
- SNHG15 expression inversely correlated with MTSS1 mRNA levels, increasing cell invasion and proliferation.
- SNHG15 directly repressed MTSS1 promoter activity.
- SNHG15, complexed with DDX5 and RTF1, interferes with RNA Polymerase II initiation at the MTSS1 core promoter, inducing transcriptional pausing.
Conclusions:
- SNHG15 acts as a molecular regulator suppressing MTSS1 transcription.
- The SNHG15-DDX5-RTF1 complex inhibits MTSS1 gene expression, potentially driving breast cancer progression.
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