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RBM38 in cancer: role and mechanism
Cheng Zou1, Ying Wan2, Lingjing He1
1College of Biology, Hunan University, Changsha, 410082, China.
Abstract:
Cancer is the second leading cause of death globally. Abnormity in gene expression regulation characterizes the trajectory of tumor development and progression. RNA-binding proteins (RBPs) are widely dysregulated, and thus implicated, in numerous human cancers. RBPs mainly regulate gene expression post-transcriptionally, but emerging studies suggest that many RBPs can impact transcription by acting on chromatin as transcription factors (TFs) or cofactors. Here, we review the evidence that RBM38, an intensively studied RBP, frequently plays a tumor-suppressive role in multiple human cancer types. Genetic studies in mice deficient in RBM38 on different p53 status also establish RBM38 as a tumor suppressor (TS). By uncovering a spectrum of transcripts bound by RBM38, we discuss the diversity in its mechanisms of action in distinct biological contexts. Examination of the genomic features and expression pattern of RBM38 in human tissues reveals that it is generally lost but rarely mutated, in cancers. By assessing future trends in the study of RBM38 in cancer, we signify the possibility of targeting RBM38 and its related pathways as therapeutic strategies against cancer.
Insights
RNA-binding protein 38 (RBM38) acts as a tumor suppressor in many cancers. Loss of RBM38 expression, not mutation, is common in cancer, suggesting RBM38 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Cancer is a leading global cause of death, often driven by dysregulated gene expression.
- RNA-binding proteins (RBPs) are frequently implicated in cancer, impacting gene regulation.
- Emerging evidence shows RBPs can influence transcription, not just post-transcriptional processes.
Purpose of the Study:
- To review the evidence for RBM38 as a tumor suppressor across various human cancers.
- To explore RBM38's diverse mechanisms of action in different biological contexts.
- To assess RBM38's genomic and expression patterns in human cancers and its therapeutic potential.
Main Methods:
- Literature review of studies on RBM38 in cancer.
- Analysis of genetic studies in RBM38-deficient mice.
- Examination of RBM38-bound transcripts and genomic data.
Main Results:
- RBM38 functions as a tumor suppressor in multiple human cancer types.
- RBM38 deficiency, particularly with specific p53 statuses, promotes tumor development.
- RBM38 binds diverse transcripts, exhibiting context-dependent regulatory mechanisms.
- RBM38 is typically lost, rather than mutated, in human cancers.
Conclusions:
- RBM38 plays a significant tumor-suppressive role in cancer.
- The loss of RBM38 expression is a common feature in cancer development.
- Targeting RBM38 and its pathways presents a promising therapeutic strategy for cancer treatment.
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