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Updated: Jun 11, 2025
Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
Global RNA Interaction and Transcriptome Profiles Demonstrate the Potential Anti-Oncogenic Targets and Pathways of
Ping Peng1, Qingqing Yin2, Wei Sun1
1Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei, China.
Background:
The fate and functions of RNAs are coordinately regulated by RNA-binding proteins (RBPs), which are often dysregulated in various cancers. Known as a splicing regulator, RNA-binding motif protein 6 (RBM6) harbors tumor-suppressor activity in many cancers; however, there is a lack of research on the molecular targets and regulatory mechanisms of RBM6.
Methods:
In this study, we constructed an RBM6 knock-down (shRBM6) model in the HeLa cell line to investigate its functions and molecular targets. Then we applied improved RNA immunoprecipitation coupled with sequencing (iRIP-seq) and whole transcriptome sequencing approaches to investigate the potential role and RNA targets of RBM6.
Results:
Using The Cancer Genome Atlas dataset, we found that higher expression of RBM6 is associated with a better prognosis in many cancer types. In addition, we found that RBM6 knockdown promoted cell proliferation and inhibited apoptosis, demonstrating that RBM6 may act as an anti-oncogenic protein in cancer cells. RBM6 can regulate the alternative splicing (AS) of genes involved in DNA damage response, proliferation, and apoptosis-associated pathways. Meanwhile, RBM6 knockdown activated type I interferon signaling pathways and inhibited the expression of genes involved in the cell cycle, cellular responses to DNA damage, and DNA repair pathways. The differentially expressed genes (DEGs) by shRBM6 and their involved pathways were likely regulated by the transcription factors undergoing aberrant AS by RBM6 knockdown. For iRIP-seq analysis, we found that RBM6 could interact with a large number of mRNAs, with a tendency for binding motifs GGCGAUG and CUCU. RBM6 bound to the mRNA of cell proliferation- and apoptosis-associated genes with dysregulated AS after RBM6 knockdown.
Conclusions:
In summary, our study highlights the important role of RBM6, as well as the downstream targets and regulated pathways, suggesting the potential regulatory mechanisms of RBM6 in the development of cancer.
Insights
RNA-binding motif protein 6 (RBM6) acts as a tumor suppressor by regulating RNA splicing and impacting cell proliferation and apoptosis. This study identifies RBM6 targets, revealing its role in cancer development.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- RNA-binding proteins (RBPs) regulate RNA fate and function, with dysregulation common in cancers.
- RNA-binding motif protein 6 (RBM6) is a known splicing regulator with tumor-suppressive activity, but its targets and mechanisms are underexplored.
Purpose of the Study:
- To investigate the functions and molecular targets of RBM6 in cancer.
- To elucidate the regulatory mechanisms of RBM6 in cancer development.
Main Methods:
- Constructed an RBM6 knock-down (shRBM6) model in HeLa cells.
- Applied improved RNA immunoprecipitation coupled with sequencing (iRIP-seq) and whole transcriptome sequencing.
- Analyzed The Cancer Genome Atlas (TCGA) dataset for RBM6 expression and patient prognosis.
Main Results:
- Higher RBM6 expression correlates with better prognosis in multiple cancer types.
- RBM6 knockdown promoted proliferation, inhibited apoptosis, and dysregulated alternative splicing (AS) of key cancer-related genes.
- RBM6 binds to numerous mRNAs, including those involved in proliferation and apoptosis, with specific motif preferences (GGCGAUG, CUCU).
- RBM6 knockdown activated type I interferon signaling and inhibited cell cycle and DNA repair pathways.
Conclusions:
- RBM6 functions as an anti-oncogenic protein by regulating alternative splicing of critical cancer-related genes.
- Identified downstream targets and pathways regulated by RBM6, providing insights into its role in cancer.
- Highlights RBM6 as a potential therapeutic target in cancer treatment.
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