MicroRNA-145-5p inhibits the tumorigenesis of breast cancer through SENP2-regulated ubiquitination of ERK2

Sep 21, 2026

Breast carcinoma shows the highest incidence among cancers in women and remains a leading cause of mortality. SUMOylation is recognized as a key regulator in breast cancer progression, yet SENP2’s function and mechanism are insufficiently defined. SENP2 was found to promote tumorigenesis in vitro and in vivo by regulating ERK2 SUMOylation, while microRNA-145-5p binds SENP2 mRNA and suppresses progression through coordinated effects on SENP2 transcription and ERK2 SUMOylation.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

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Abstract

Introduction

Breast cancer background and therapeutic challenge

SUMOylation pathway and role of SENP2

ERK2 function and therapeutic relevance

Non-coding RNAs and rationale for miR-145-5p

Cellular and Molecular Life Sciences (2024) 81:461 [https://doi.org/10.1007/s00018-024-05505-8](https://doi.org/10.1007/s00018-024-05505-8) Cellular and Molecular Life Sciences ORIGINAL ARTICLE MicroRNA-145-5p inhibits the tumorigenesis of breast cancer through SENP2-regulated ubiquitination of ERK2 Xu Chen1 · Danqing Li1 · Qi Su1 · Xing Ling1 · Siyu Ding1 · Runxiao Xu1 · Zhaoxia Liu1 · Yuanyuan Qin1 · Jinping Zhang2 · Zhihui Yang2 · Xunlei Kang3 · Yitao Qi1 · Hongmei Wu1 Received: 13 July 2024 / Revised: 4 October 2024 / Accepted: 11 November 2024 © The Author(s) 2024 Abstract Breast carcinoma exhibits the highest incidence among various cancers and is the foremost cause of mortality in women. Increasing evidence shows that SUMOylation of proteins plays a critical role in the progression of breast cancer; however, the role of SENP2 and its molecular mechanism in breast cancer remain underexplored. Here, we discerned that SENP2 promoted the tumorigenesis of breast cancer both in vitro and in vivo. Furthermore, we identified that ERK2 was SUMOylated and that SENP2 played a role by deconjugating ERK2 SUMOylation in breast cancer. SUMOylation of ERK2 promoted its ubiquitin-proteasomal degradation, thus inhibiting the epithelial-to-mesenchymal transition in breast cancer cells. Furthermore, microRNA-145-5p (miR-145-5p) has emerged as a scarce commodity in breast cancer and binds to the 3’-untranslated region of SENP2 mRNA to govern the regulatory dynamics of SENP2 expression. Finally, miR-145-5p inhibits SENP2 transcription, enhances ERK2 SUMOylation, and ultimately suppresses the progression of breast cancer. These revelations suggest evolving ideas for the miR-145-5p-SENP2 axis in therapeutic intervention, thus heralding transformative prospects for the clinical management of breast cancer. Keywords SENP2 · ERK2 · MicroRNA-145-5p · SUMOylation · Breast cancer Introduction Breast carcinoma is the most prevalent malignancy afflicting women worldwide and comprises 15% of new cancer cases in China [1] and 30% of new female cancer cases in America [2], which poses a severe threat to the health of women. Breast cancer, marked by its heterogeneity, is rooted in histological attributes, delineating four distinct Xu Chen, Danqing Li and Qi Su contributed equally to this work. 􀀍 Yitao Qi [qiyitao@snnu.edu.cn](qiyitao@snnu.edu.cn) 􀀍 Hongmei Wu [hq8479@snnu.edu.cn](hq8479@snnu.edu.cn) 1 College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, China 2 Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 3 Center for Precision Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA subtypes, including luminalA, luminal B, human epidermal growth factor receptor 2 (HER2)-positive, and notorious triple-negative breast cancer (TNBC) [3] . TNBC, due to its high metastasis and aggressiveness, has a survival rate of only 14% among advanced patients [4] . Although current therapies for breast cancer are diversified, the cure rate is still low due to drug resistance. Therefore, the exploration of new therapeutic targets has been the focus of breast cancer research. Intriguingly, we found that small ubiquitin-like modifier (SUMO) proteins constitute a distinctive class within the proteomic landscape [5] . The journey of a SUMO protein precursor is cleaved and then followed by maturation under the catalytic guidance of SUMO-specific protease (SENP), activated by the activating enzyme, transitioning to the conjugating enzyme before culminating in its ligation to the designated target protein, under the meticulous orchestration of the ligating enzyme [6] . SUMOylation, characterized by its multifaceted modulatory potential, functions as an essential regulator governing an array of physiological and pathological processes [7] . A constellation of six SENPs, each endowed with distinct substrate specificities, 1 3 col

FAQs

What role does SENP2 play in breast cancer tumorigenesis?

SENP2 promotes the tumorigenesis of breast cancer both in vitro and in vivo by regulating ERK2 SUMOylation.

How does microRNA-145-5p affect SENP2 expression?

MicroRNA-145-5p binds to the 3’-untranslated region of SENP2 mRNA, suppressing SENP2 expression.

How does miR-145-5p ultimately suppress breast cancer progression?

miR-145-5p inhibits SENP2 transcription, enhances ERK2 SUMOylation, and suppresses breast cancer progression through this regulatory axis.

Sep 21, 2026

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