Angioregulatory microRNAs in Colorectal Cancer

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Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Angiogenesis is a rate-determining step in CRC development and metastasis. The balance of angiogenic and antiangiogenic factors is crucial in this process. Angiogenesis-related genes can be regulated post-transcriptionally by microRNAs (miRNAs) and some miRNAs have been shown to shuttle between tumor cells and the tumor microenvironment (TME). MiRNAs have context-dependent actions and can promote or suppress angiogenesis dependent on the type of cancer. On the one hand, miRNAs downregulate anti-angiogenic targets and lead to angiogenesis induction. Tumor suppressor miRNAs, on the other hand, enhance anti-angiogenic response by targeting pro-angiogenic factors. Understanding the interaction between these miRNAs and their target mRNAs will help to unravel molecular mechanisms involved in CRC progression. The aim of this article is to review the current literature on angioregulatory miRNAs in CRC.

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MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice.

Angelika Bonauer, Guillaume Carmona, Masayoshi Iwasaki … (2009)

MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Here, we show that the miR-17approximately92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis). Forced overexpression of miR-92a in endothelial cells blocked angiogenesis in vitro and in vivo. In mouse models of limb ischemia and myocardial infarction, systemic administration of an antagomir designed to inhibit miR-92a led to enhanced blood vessel growth and functional recovery of damaged tissue. MiR-92a appears to target mRNAs corresponding to several proangiogenic proteins, including the integrin subunit alpha5. Thus, miR-92a may serve as a valuable therapeutic target in the setting of ischemic disease.

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Exosomes in cancer: small particle, big player

Xu Zhang, Xiao Shuai Yuan, Hui Shi … (2015)

Exosomes have emerged as a novel mode of intercellular communication. Exosomes can shuttle bioactive molecules including proteins, DNA, mRNA, as well as non-coding RNAs from one cell to another, leading to the exchange of genetic information and reprogramming of the recipient cells. Increasing evidence suggests that tumor cells release excessive amount of exosomes, which may influence tumor initiation, growth, progression, metastasis, and drug resistance. In addition, exosomes transfer message from tumor cells to immune cells and stromal cells, contributing to the escape from immune surveillance and the formation of tumor niche. In this review, we highlight the recent advances in the biology of exosomes as cancer communicasomes. We review the multifaceted roles of exosomes, the small secreted particles, in communicating with other cells within tumor microenvironment. Given that exosomes are cell type specific, stable, and accessible from body fluids, exosomes may provide promising biomarkers for cancer diagnosis and represent new targets for cancer therapy.

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Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function

Yin C Hu, Shan-Shan Rao, Zhen-Xing Wang … (2018)

The application of blood plasma for soft tissue wound healing is receiving much more attention recently. Exosomes are critical paracrine mediators that can be obtained from biological fluids including plasma and be able to induce regenerative effects by transferring bioactive molecules such as microRNAs (miRNAs). This study aimed to investigate the effects of exosomes from human umbilical cord blood plasma (UCB-Exos) on wound healing and to elucidate the underlying mechanism. Methods: UCB-Exos were isolated by ultracentrifugation and subcutaneously injected into full-thickness skin wounds in mice. The efficacy of UCB-Exos on wound healing was evaluated by measuring wound closure rates, histological analysis and immunofluorescence examinations. In vitro, quantitative real-time PCR (qRT-PCR) analysis was performed to detect the expression levels of a class of miRNAs that have positive roles in regulating wound healing. The scratch wound assay, transwell assay and cell counting kit-8 analysis were conducted to assess the effects of UCB-Exos on migration and proliferation of human skin fibroblasts and endothelial cells. Tube formation assay was carried out to test the impact of UCB-Exos on angiogenic tube formation ability of endothelial cells. Meanwhile, by using specific RNA inhibitors or siRNAs, the roles of the candidate miRNA and its target genes in UCB-Exos-induced regulation of function of fibroblasts and endothelial cells were assessed. Results: The local transplantation of UCB-Exos into mouse skin wounds resulted in accelerated re-epithelialization, reduced scar widths, and enhanced angiogenesis. In vitro, UCB-Exos could promote the proliferation and migration of fibroblasts, and enhance the angiogenic activities of endothelial cells. Notably, miR-21-3p was found to be highly enriched in UCB-Exos and served as a critical mediator in UCB-Exos -induced regulatory effects through inhibition of phosphatase and tensin homolog (PTEN) and sprouty homolog 1 (SPRY1). Conclusion: Our results suggest that UCB-Exos are important effectors of plasma activity and can be used as a novel promising strategy for soft tissue wound healing.

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Journal

Journal ID (nlm-ta): Cancers (Basel)

Journal ID (iso-abbrev): Cancers (Basel)

Journal ID (publisher-id): cancers

Title: Cancers

Publisher: MDPI

ISSN (Electronic): 2072-6694

Publication date (Electronic): 26 December 2019

Publication date Collection: January 2020

Volume: 12

Issue: 1

Electronic Location Identifier: 71

Affiliations

[1 ]Research Center for Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan 65178, Iran; soheilih@ 123456gmail.com (M.H.S.); sjam110@ 123456yahoo.com (M.S.)

[2 ]Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria; michael.grusch@ 123456meduniwien.ac.at

[3 ]Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute Academic Center for Education, Culture and Research (ACECR), Tehran 1315795613, Iran; hodakeshmiri@ 123456ut.ac.ir

[4 ]Department of Medical Genetics, and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada; hmaadi@ 123456ualberta.ca

Author notes

[* ]Correspondence: Aminra14@ 123456gmail.com (R.A.); zhixiang.wang@ 123456ualberta.ca (Z.W.)

Author information

Mohammad Hasan Soheilifar https://orcid.org/0000-0002-1359-2944

Michael Grusch https://orcid.org/0000-0001-5486-9340

Hoda Keshmiri Neghab https://orcid.org/0000-0003-1895-6695

Zhixiang Wang https://orcid.org/0000-0002-6364-6891

Article

Publisher ID: cancers-12-00071

DOI: 10.3390/cancers12010071

PMC ID: 7016698

PubMed ID: 31887997

SO-VID: f3bebc5b-ea9b-461f-950a-3c6ceafcd16f

License:

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/).

History

Date received : 05 December 2019

Date accepted : 23 December 2019

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Angioregulatory microRNAs in Colorectal Cancer

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Cancer Metabolism

Most cited references 165

MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice.

Exosomes in cancer: small particle, big player

Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function

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