Aberrant regulation of CXCR4 in cancer via deviant microRNA-targeted interactions
Alexei J Stuckel1, Tripti Khare1, Marc Bissonnette2
1Department of Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri 65212, USA.
Abstract:
CXCR4 is involved in many facets of cancer, including being a major player in establishing metastasis. This is in part due to the deregulation of CXCR4, which can be attributed to many genetic and epigenetic mechanisms, including aberrant microRNA-CXCR4 interaction. MicroRNAs (miRNAs) are a type of small non-coding RNA that primarily targets the 3' UTR of mRNA transcripts, which in turn suppresses mRNA and subsequent protein expression. In this review, we reported and characterized the many aberrant miRNA-CXCR4 interactions that occur throughout human cancers. In particular, we reported known target sequences located on the 3' UTR of CXCR4 transcripts that tumour suppressor miRNAs bind and therefore regulate expression by. From these aberrant interactions, we also documented affected downstream genes/pathways and whether a particular tumour suppressor miRNA was reported as a prognostic marker in its respected cancer type. In addition, a limited number of cancer-causing miRNAs coined 'oncomirs' were reported and described in relation to CXCR4 regulation. Moreover, the mechanisms underlying both tumour suppressor and oncomir deregulations concerning CXCR4 expression were also explored. Furthermore, the miR-146a-CXCR4 axis was delineated in oncoviral infected endothelial cells in the context of virus-causing cancers. Lastly, miRNA-driven therapies and CXCR4 antagonist drugs were discussed as potential future treatment options in reported cancers pertaining to deregulated miRNA-CXCR4 interactions.
Insights
Aberrant microRNA (miRNA) interactions with CXCR4 are key in cancer metastasis. This review details these interactions, highlighting their role in cancer progression and potential therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- CXCR4 plays a critical role in cancer metastasis through its deregulation.
- Aberrant microRNA (miRNA)-CXCR4 interactions are significant contributors to cancer development.
- MicroRNAs regulate gene expression by targeting messenger RNA (mRNA) 3' untranslated regions (UTRs).
Approach:
- This review characterizes aberrant miRNA-CXCR4 interactions across various human cancers.
- It identifies specific miRNA binding sites on the CXCR4 3' UTR and their regulatory effects.
- The study examines downstream pathways, prognostic significance of miRNAs, and the role of oncomirs.
Key Points:
- Tumor suppressor miRNAs binding to CXCR4's 3' UTR regulate its expression.
- Deregulation of both tumor suppressor miRNAs and oncomirs impacts CXCR4 expression.
- The miR-146a-CXCR4 axis is implicated in virus-associated cancers.
Conclusions:
- Understanding miRNA-CXCR4 interactions is crucial for cancer research.
- Dysregulated miRNA-CXCR4 interactions offer potential therapeutic targets.
- miRNA-based therapies and CXCR4 antagonists represent future treatment avenues.
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