mRNA modification orchestrates cancer stem cell fate decisions
Weicheng Liang1,2,3, Zexiao Lin2,4, Cong Du2,3
1Vaccine Research Institute, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
Abstract:
Despite their small numbers, cancer stem cells play a central role in driving cancer cell growth, chemotherapeutic resistance, and distal metastasis. Previous studies mainly focused on how DNA or histone modification determines cell fate in cancer. However, it is still largely unknown how RNA modifications orchestrate cancer cell fate decisions. More than 170 distinct RNA modifications have been identified in the RNA world, while only a few RNA base modifications have been found in mRNA. Growing evidence indicates that three mRNA modifications, inosine, 5-methylcytosine, and N6-methyladenosine, are essential for the regulation of spatiotemporal gene expression during cancer stem cell fate transition. Furthermore, transcriptome-wide mapping has found that the aberrant deposition of mRNA modification, which can disrupt the gene regulatory network and lead to uncontrollable cancer cell growth, is widespread across different cancers. In this review, we try to summarize the recent advances of these three mRNA modifications in maintaining the stemness of cancer stem cells and discuss the underlying molecular mechanisms, which will shed light on the development of novel therapeutic approaches for eradicating cancer stem cells.
Insights
RNA modifications, including inosine, 5-methylcytosine, and N6-methyladenosine, are crucial for cancer stem cell fate. Aberrant mRNA modifications drive cancer growth and metastasis, offering new therapeutic targets.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Cancer stem cells (CSCs) drive tumor growth, metastasis, and therapy resistance.
- Research has focused on DNA/histone modifications, with limited understanding of RNA modifications in CSC fate.
- Over 170 RNA modifications exist, but only a few mRNA modifications are well-studied.
Purpose of the Study:
- To review recent advances in three key mRNA modifications: inosine, 5-methylcytosine, and N6-methyladenosine.
- To discuss the molecular mechanisms by which these mRNA modifications maintain CSC stemness.
- To highlight the potential of targeting mRNA modifications for novel cancer therapies.
Main Methods:
- Literature review of recent studies on mRNA modifications in cancer.
- Analysis of transcriptome-wide mapping data for aberrant mRNA modification deposition.
- Synthesis of current knowledge on molecular pathways linking mRNA modifications to CSC fate.
Main Results:
- Inosine, 5-methylcytosine, and N6-methyladenosine are essential for CSC fate regulation.
- Aberrant mRNA modification patterns are widespread across various cancers.
- These modifications disrupt gene regulatory networks, promoting uncontrolled cancer cell proliferation.
Conclusions:
- Targeting specific mRNA modifications offers a promising strategy for eradicating CSCs.
- Understanding these RNA modifications is key to developing novel anti-cancer therapeutics.
- Further research into RNA modification mechanisms can illuminate CSC-driven cancer progression.
More Related Videos
Related Concept Videos
02:40Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
01:01Regulation of Hematopoietic Stem Cells
01:19Mesenchymal Stem Cells
01:22MicroRNAs
01:22MicroRNAs
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...