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Published on: August 2, 2024
R-loop accumulation promotes OSCC malignant progression by upregulating MARVELD3 expression
Xinyi Li1, Xuerong Xiang1, Jiao Huang1
1The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing 401147, China; Chongqing Key Laboratory of Oral Diseases, Chongqing 401147, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China.
Objective:
The R-loop is known to play a critical role in the progression of various cancers, yet its involvement in OSCC remains unexplored. This study aims to investigate the role and mechanism of R-loop-mediated MARVELD3 in OSCC.
Methods:
DRIP-seq was employed to assess the involvement of the R-loop in OSCC progression. RT-PCR, IHC, and immunofluorescence were utilized to measure MARVELD3 expression and the relationship with R-loop. The functional role of MARVELD3 in OSCC was investigated through proliferation assays, colony formation assays, Transwell assays, and flow cytometry. The regulatory mechanism underlying MARVELD3 was further investigated using RNA-seq, western blotting, and quantitative PCR (qPCR).
Results:
Dysregulation of R-loop-mediated genes holds significant biological relevance in OSCC. MARVELD3 was found to be highly expressed in OSCC cells due to R-loop accumulation; knockdown of MARVELD3 led to reduced proliferation, migration, and invasion, while MARVELD3 overexpression enhanced these characteristics. Mechanistically, MARVELD3 promotes the MAPK signaling pathway by suppressing the expression of TTC9.
Conclusion:
In conclusion, R-loop accumulation promotes transcription of the MARVELD3. MARVELD3 exerts a tumor-promoting effect in OSCC by downregulating TTC9 and activating the MAPK signaling pathway.
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