microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review

Roberta Giordo; Fatemeh Abdullah M Ahmadi; Nedal Al Husaini; Noora Rashid A M Al-Nuaimi; Salma M S Ahmad; Gianfranco Pintus; Hatem Zayed

doi:10.1016/j.ncrna.2024.03.013

microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review

Noncoding RNA Res. 2024 Mar 31;9(3):831-852. doi: 10.1016/j.ncrna.2024.03.013. eCollection 2024 Sep.

Authors

Roberta Giordo¹, Fatemeh Abdullah M Ahmadi², Nedal Al Husaini², Noora Rashid A M Al-Nuaimi², Salma M S Ahmad², Gianfranco Pintus^{1

3}, Hatem Zayed²

Affiliations

¹ Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100, Sassari, Italy.
² Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, P.O. Box 2713, Doha, Qatar.
³ Department of Medical Laboratory Sciences, College of Health Sciences and Sharjah Institute for Medical Research, University of Sharjah, University City Rd, Sharjah, 27272, United Arab Emirates.

Abstract

Non-coding RNAs (ncRNAs) are a diverse group of functional RNA molecules that lack the ability to code for proteins. Despite missing this traditional role, ncRNAs have emerged as crucial regulators of various biological processes and have been implicated in the development and progression of many diseases, including cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two prominent classes of ncRNAs that have emerged as key players in cancer pathophysiology. In particular, miR-21 has been reported to exhibit oncogenic roles in various forms of human cancer, including prostate, breast, lung, and colorectal cancer. In this context, miR-21 overexpression is closely associated with tumor proliferation, growth, invasion, angiogenesis, and chemoresistance, whereas miR-21 inactivation is linked to the regression of most tumor-related processes. Accordingly, miR-21 is a crucial modulator of various canonical oncogenic pathways such as PTEN/PI3K/Akt, Wnt/β-catenin, STAT, p53, MMP2, and MMP9. Moreover, interplays between lncRNA and miRNA further complicate the regulatory mechanisms underlying tumor development and progression. In this regard, several lncRNAs have been found to interact with miR-21 and, by functioning as competitive endogenous RNAs (ceRNAs) or miRNA sponges, can modulate cancer tumorigenesis. This work presents and discusses recent findings highlighting the roles and pathophysiological implications of the miR-21-lncRNA regulatory axis in cancer occurrence, development, and progression. The data collected indicate that specific lncRNAs, such as MEG3, CASC2, and GAS5, are strongly associated with miR-21 in various types of cancer, including gastric, cervical, lung, and glioma. Indeed, these lncRNAs are well-known tumor suppressors and are commonly downregulated in different types of tumors. Conversely, by modulating various mechanisms and oncogenic signaling pathways, their overexpression has been linked with preventing tumor formation and development. This review highlights the significance of these regulatory pathways in cancer and their potential for use in cancer therapy as diagnostic and prognostic markers.

Keywords: Cancer; Regulatory axis; ceRNAs; lncRNAs; miRNAs.

Publication types

Review