Obesity, Insulin Resistance, and Colorectal Cancer: Could miRNA Dysregulation Play a Role?

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Abstract

Obesity is associated with insulin resistance and low-grade inflammation. Insulin resistance is a risk factor for cancer. A recent chapter in epigenetics is represented by microRNAs (miRNAs), which post-transcriptionally regulate gene expression. Dysregulated miRNA profiles have been associated with diseases including obesity and cancer. Herein we report dysregulated miRNAs in obesity both in animal models and in humans, and we also document dysregulated miRNAs in colorectal cancer (CRC), as example of an obesity-related cancer. Some of the described miRNAs are found to be similarly dysregulated both in obesity, insulin resistance (IR), and CRC. Thus, we present miRNAs as a potential molecular link between obesity and CRC onset and development, giving a new perspective on the role of miRNAs in obesity-associated cancers.

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Most cited references 105

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Adipocytes as regulators of energy balance and glucose homeostasis.

Evan Rosen, Bruce M Spiegelman (2006)

Adipocytes have been studied with increasing intensity as a result of the emergence of obesity as a serious public health problem and the realization that adipose tissue serves as an integrator of various physiological pathways. In particular, their role in calorie storage makes adipocytes well suited to the regulation of energy balance. Adipose tissue also serves as a crucial integrator of glucose homeostasis. Knowledge of adipocyte biology is therefore crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. Furthermore, the rational manipulation of adipose physiology is a promising avenue for therapy of these conditions.

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Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

E Bandres, E Cubedo, X Agirre … (2006)

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the potential involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. In our study, we examined by Real-Time PCR the expression of 156 mature miRNA in colorectal cancer. The analysis by several bioinformatics algorithms of colorectal tumours and adjacent non-neoplastic tissues from patients and colorectal cancer cell lines allowed identifying a group of 13 miRNA whose expression is significantly altered in this tumor. The most significantly deregulated miRNA being miR-31, miR-96, miR-133b, miR-135b, miR-145, and miR-183. In addition, the expression level of miR-31 was correlated with the stage of CRC tumor. Our results suggest that miRNA expression profile could have relevance to the biological and clinical behavior of colorectal neoplasia.

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An estimate of the total number of true human miRNAs

Julia Alles, Tobias Fehlmann, Ulrike Fischer … (2019)

Abstract While the number of human miRNA candidates continuously increases, only a few of them are completely characterized and experimentally validated. Toward determining the total number of true miRNAs, we employed a combined in silico high- and experimental low-throughput validation strategy. We collected 28 866 human small RNA sequencing data sets containing 363.7 billion sequencing reads and excluded falsely annotated and low quality data. Our high-throughput analysis identified 65% of 24 127 mature miRNA candidates as likely false-positives. Using northern blotting, we experimentally validated miRBase entries and novel miRNA candidates. By exogenous overexpression of 108 precursors that encode 205 mature miRNAs, we confirmed 68.5% of the miRBase entries with the confirmation rate going up to 94.4% for the high-confidence entries and 18.3% of the novel miRNA candidates. Analyzing endogenous miRNAs, we verified the expression of 8 miRNAs in 12 different human cell lines. In total, we extrapolated 2300 true human mature miRNAs, 1115 of which are currently annotated in miRBase V22. The experimentally validated miRNAs will contribute to revising targetomes hypothesized by utilizing falsely annotated miRNAs.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 14 June 2019

Publication date Collection: June 2019

Volume: 20

Issue: 12

Electronic Location Identifier: 2922

Affiliations

Department of Mother and Child, 42123 Azienda USL–IRCCS di Reggio Emilia, Italy; francesca.cirillo@ 123456ausl.re.it (F.C.); cecilia.catellani@ 123456ausl.re.it (C.C.); chiara.sartori@ 123456ausl.re.it (C.S.); pietro.lazzeroni@ 123456ausl.re.it (P.L.); sergio.amarri@ 123456ausl.re.it (S.A.)

Author notes

[* ]Correspondence: mariaelisabeth.street@ 123456ausl.re.it ; Tel.: +0039-052-2296-194

[†]

These authors contributed equally to this work.

Author information

Francesca Cirillo https://orcid.org/0000-0003-2183-4226

Cecilia Catellani https://orcid.org/0000-0002-6354-9979

Chiara Sartori https://orcid.org/0000-0001-5980-9160

Maria Elisabeth Street https://orcid.org/0000-0001-8427-8971

Article

Publisher ID: ijms-20-02922

DOI: 10.3390/ijms20122922

PMC ID: 6628223

PubMed ID: 31207998

SO-VID: 762e6f90-7e93-4423-a899-39d90c5dfffc

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Obesity, Insulin Resistance, and Colorectal Cancer: Could miRNA Dysregulation Play a Role?

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Karger: Oncology

Most cited references 105

Adipocytes as regulators of energy balance and glucose homeostasis.

Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

An estimate of the total number of true human miRNAs

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