Regulation and Function of Microrna-152 in Various Types of Cancers: Its Upstream Regulators and Downstream Targets Publisher Pubmed



S Jafarzadeh SARA ; Aa Jafarzaheh Abdollah A ; R Zandvakili RAZIYEH ; M Nemati MARYAM ; A Jafari AMENEH ; M Morshedi MOHAMMADMATIN ; F Divani FATEMEH ; Hr Mirzaei Hamed REZA
Source: Clinical and Experimental Medicine Published:2025

Abstract

MicroRNAs (miRNAs) are key regulators of gene expression that bind to the 3′-untranslated region (3′-UTR) of target mRNAs, modulating protein expression and influencing cancer progression. Among these, microRNA-152 (miR-152) is frequently downregulated in diverse malignancies—including breast, endometrial, gastrointestinal, and hematologic cancers—primarily due to promoter hypermethylation. This epigenetic silencing, mediated by DNMT1, is compounded by competitive sponging from long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), forming intricate regulatory networks. Functionally, miR-152 acts as a tumor suppressor by targeting oncogenic pathways such as PI3K/AKT/mTOR, EMT drivers, and chemoresistance mediators. However, its role is context-dependent, exhibiting dual oncogenic and suppressive effects in prostate cancer and certain leukemias. Therapeutically, restoring miR-152 expression via mimics, demethylating agents, or nanocarrier-based delivery systems shows promise in preclinical studies for reversing chemoresistance and inhibiting metastasis. This review synthesizes miR-152’s upstream regulators, downstream targets, and clinical potential, offering a roadmap for its exploitation in precision oncology. © 2025 Elsevier B.V., All rights reserved.