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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
Noncoding RNAs regulate alternative splicing in Cancer
Yunze Liu1,2, Xin Liu3, Changwei Lin4
1Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Abstract:
AS (alternative splicing) is a fundamental process by which a gene can generate multiple distinct mRNA transcripts to increase protein diversity. Defects in AS influence the occurrence and development of many diseases, including cancers, and are frequently found to participate in various aspects of cancer biology, such as promoting invasion, metastasis, apoptosis resistance and drug resistance. NcRNAs (noncoding RNAs) are an abundant class of RNAs that do not encode proteins. NcRNAs include miRNAs (microRNAs), lncRNAs (long noncoding RNAs), circRNAs (circular RNAs) and snRNAs (small nuclear RNAs) and have been proven to act as regulatory molecules that mediate cancer processes through AS. NcRNAs can directly or indirectly influence a plethora of molecular targets to regulate cis-acting elements, trans-acting factors, or pre-mRNA transcription at multiple levels, affecting the AS process and generating alternatively spliced isoforms. Consequently, ncRNA-mediated AS outcomes affect multiple cellular signaling pathways that promote or suppress cancer progression. In this review, we summarize the current mechanisms by which ncRNAs regulate AS in cancers and discuss their potential clinical applications as biomarkers and therapeutic targets.
Insights
Alternative splicing (AS) defects drive cancer progression. Noncoding RNAs (ncRNAs) regulate AS in cancer, influencing invasion, metastasis, and drug resistance, offering potential as biomarkers and therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- Alternative splicing (AS) generates protein diversity but its defects are implicated in cancer.
- Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, are key regulators in biological processes.
- Dysregulation of AS is a hallmark of cancer, contributing to tumorigenesis and progression.
Purpose of the Study:
- To review mechanisms of ncRNA-mediated regulation of AS in cancer.
- To explore the role of ncRNA-regulated AS in cancer hallmarks like invasion and drug resistance.
- To discuss the clinical potential of ncRNA-AS interactions as cancer biomarkers and therapeutic targets.
Main Methods:
- Literature review of studies on ncRNAs, AS, and cancer.
- Analysis of molecular mechanisms by which ncRNAs influence AS.
- Synthesis of evidence linking ncRNA-AS pathways to cancer progression and clinical outcomes.
Main Results:
- NcRNAs modulate AS by targeting regulatory factors and pre-mRNA.
- Altered AS isoforms driven by ncRNAs contribute to cancer hallmarks.
- Specific ncRNA-AS interactions are associated with cancer invasion, metastasis, and therapy resistance.
Conclusions:
- NcRNAs play a critical role in regulating AS in the context of cancer.
- Targeting ncRNA-AS pathways presents promising avenues for cancer diagnostics and therapeutics.
- Further research is needed to fully elucidate and translate these findings into clinical practice.
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