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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
The p53/microRNA connection in gastrointestinal cancer
Matjaz Rokavec1, Huihui Li1, Longchang Jiang1
1Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.
Abstract:
The protein encoded by the TP53 gene is one of the most important suppressors of tumor formation, which is also frequently inactivated in gastrointestinal cancer. MicroRNAs (miRNAs) are small noncoding RNAs that inhibit translation and/or promote degradation of their target messenger RNAs. In recent years, several miRNAs have been identified as mediators and regulators of p53's tumor suppressing functions. p53 induces expression and/or maturation of several miRNAs, which leads to the repression of critical effector proteins. Furthermore, certain miRNAs regulate the expression and activity of p53 through direct repression of p53 or its regulators. Experimental findings indicate that miRNAs are important components of the p53 network. In addition, the frequent genetic and epigenetic alterations of p53-regulated miRNAs in tumors indicate that they play an important role in cancer initiation and/or progression. Therefore, p53-regulated miRNAs may represent attractive diagnostic and/or prognostic biomarkers. Moreover, restoration of p53-induced miRNAs results in suppression of tumor growth and metastasis in mouse models of cancer. Thus, miRNA-based therapeutics may represent a feasible strategy for future cancer treatment. Here we summarize the current published state-of-the-art on the role of the p53-miRNA connection in gastrointestinal cancer.
Insights
The tumor suppressor protein p53 and microRNAs (miRNAs) form a critical network in gastrointestinal cancer. Understanding this p53-miRNA connection offers potential for novel cancer diagnostics and therapeutics.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The TP53 gene product, a key tumor suppressor, is often inactivated in gastrointestinal cancers.
- MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression post-transcriptionally.
- The interplay between p53 and miRNAs is crucial for tumor suppression and cancer progression.
Purpose of the Study:
- To review the current understanding of the p53-miRNA axis in gastrointestinal cancer.
- To highlight the role of p53-regulated miRNAs in cancer initiation and progression.
- To explore the potential of p53-miRNAs as diagnostic/prognostic biomarkers and therapeutic targets.
Main Methods:
- Literature review of studies investigating the p53-miRNA network in gastrointestinal cancer.
- Analysis of experimental findings on miRNA regulation by p53 and vice versa.
- Evaluation of the clinical implications of p53-miRNA alterations in tumors.
Main Results:
- p53 influences miRNA expression and maturation, impacting downstream targets.
- Certain miRNAs directly regulate p53 or its associated proteins.
- Alterations in p53-regulated miRNAs are common in gastrointestinal tumors, affecting cancer development.
- Restoring p53-induced miRNAs inhibits tumor growth and metastasis in preclinical models.
Conclusions:
- The p53-miRNA network is integral to gastrointestinal cancer biology.
- p53-regulated miRNAs show promise as biomarkers for diagnosis and prognosis.
- miRNA-based therapies targeting the p53 network represent a potential future treatment strategy for gastrointestinal cancers.
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