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Published on: June 15, 2019
Functional interplay between YY1 and CARM1 promotes oral carcinogenesis
Amit K Behera1, Manoj Kumar1, Muthu K Shanmugam2
1Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India.
Coactivator associated arginine methyltransferase 1 (CARM1) drives oral cancer by upregulating YY1. This positive feedback loop between CARM1 and YY1 promotes tumor progression, proliferation, and metastasis.
Area of Science:
- Molecular Biology
- Oncology
- Epigenetics
Background:
- Coactivator associated arginine methyltransferase 1 (CARM1) is implicated in pluripotency, differentiation, and tumorigenesis.
- CARM1 exhibits oncogenic functions in colorectal and breast cancers, often due to overexpression.
- The mechanisms driving CARM1 dysregulation in cancer remain largely unelucidated.
Purpose of the Study:
- To investigate the role of CARM1 in oral cancer.
- To identify regulatory mechanisms of CARM1 expression in oral cancer.
- To explore the functional relationship between CARM1 and YY1 in oral cancer progression.
Main Methods:
- Analysis of CARM1 and YY1 expression in oral cancer tissues and cell lines.
- Gene silencing experiments (YY1) in oral cancer cell lines.
- Cell line-based assays and xenograft studies to assess neoplastic functions.
- Transcriptomics analysis and qRT-PCR for gene expression profiling.
- In vivo reporter gene assays to study CARM1-YY1 interaction.
Main Results:
- CARM1 is overexpressed in oral cancer, exhibiting an oncogenic function.
- YY1 acts as a positive regulator of CARM1 gene expression and is overexpressed in oral cancer.
- YY1 demonstrates pro-neoplastic functions, including promoting proliferation, angiogenesis, and metastasis.
- CARM1 methylates YY1, enhancing YY1-mediated reporter gene activation.
- A positive feedback loop exists between CARM1 and YY1, driving oral cancer progression.
Conclusions:
- CARM1 and YY1 form a positive feedback loop that promotes oral cancer development and progression.
- Targeting the CARM1-YY1 axis represents a potential therapeutic strategy for oral cancer.
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