Unveiling the Role of tRNA-derived Small RNAs in MAPK Signaling Pathway: Implications for Cancer and Beyond

Sep 21, 2026

tRNA-derived small RNAs (tsRNAs) are small non-coding RNAs generated from mature or precursor tRNAs, typically spanning 14–30 nt. The MAPK signaling pathway coordinates major cellular decisions including proliferation, differentiation, survival, apoptosis, and transformation. This review links tsRNAs to MAPK regulation through protein targeting, summarizing MAPK-linked tsRNAs reported in gastric cancer and high-grade serous ovarian cancer and extending KEGG-supported roles across multiple non-cancer diseases, including varicose vein risk, spinal cord injury, diabetes-related disorders, keloid formation, intervertebral disk degeneration, systemic lupus erythematosus, lupus nephritis, acute lung injury, and more.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Overview of MAPK signaling cascade

MAPK pathway components and upstream regulators

tRNA-derived small RNAs (tsRNAs) subclasses and gene regulation

TYPE Review PUBLISHED 26 March 2024 DOI 10.3389/fgene.2024.1346852 OPEN ACCESS EDITED BY Subhashree Nayak, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH), United States REVIEWED BY Jiangxin Wang, Shenzhen University, China Amrita Singh, Yale University, United States *CORRESPONDENCE Shiwei Duan, [duansw@hzcu.edu.cn](duansw@hzcu.edu.cn) †These authors have contributed equally to this work RECEIVED 30 November 2023 ACCEPTED 13 March 2024 PUBLISHED 26 March 2024 CITATION Wang Q, Huang Q, Ying X, Shen J and Duan S (2024), Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond. Front. Genet. 15:1346852 . doi: 10.3389/fgene.2024.1346852 COPYRIGHT © 2024 Wang, Huang, Ying, Shen and Duan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond Qurui Wang 1†, Qinyuan Huang 1†, Xiaowei Ying 1, Jinze Shen 1 and Shiwei Duan 1,2* 1Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China, 2Department of Clinical Medicine, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs originating from mature or precursor tRNAs (pre-tRNA), typically spanning 14 to 30 nt. The Mitogen-activated protein kinases (MAPK) pathway orchestrates cellular responses, inﬂuencing proliferation, differentiation, apoptosis, and transformation. tsRNAs inﬂuence the expression of the MAPK signaling pathway by targeting speciﬁc proteins within the pathway. Presently, four MAPK-linked tsRNAs have implications in gastric cancer (GC) and high-grade serous ovarian cancer (HGSOC) . Notably, tRF-Glu-TTC-027 and tRF-Val-CAC- 016 modulate MAPK-related protein expression, encompassing p38, Myc, ERK, CyclinD1, CyclinB, and c-Myc, hindering GC progression via MAPK pathway inhibition. Moreover, tRF-24-V29K9UV3IU and tRF-03357 remain unexplored in speciﬁc mechanisms. KEGG analysis posits varied tsRNAs in MAPK pathway modulation for diverse non-cancer maladies. Notably, high tRF-36-F900BY4D84KRIME and tRF-23-87R8WP9IY expression relates to varicose vein (VV) risk. Elevated tiRNA-Gly-GCC-001, tRF-Gly-GCC-012, tRF-Gly-GCC- 013, and tRF-Gly-GCC-016 target spinal cord injury (SCI)-related brain-derived neurotrophic factor (BDNF), inﬂuencing MAPK expression. tRF-Gly-CCC- 039 associates with diabetes foot sustained healing, while tRF-5014a inhibits autophagy-linked ATG5 in diabetic cardiomyopathy (DCM) . Additionally, tsRNA- 14783 inﬂuences keloid formation by regulating M2 macrophage polarization. Upregulation of tRF-Arg-ACG-007 and downregulation of tRF-Ser-GCT-008 are associated with diabetes. tsRNA-04002 alleviates Intervertebral disk degeneration (IDD) by targeting PRKCA. tsRNA-21109 alleviates Systemic lupus erythematosus (SLE) by inhibiting macrophage M1 polarization. The upregulated tiNA-Gly-GCC-002 and the downregulated tRF-Ala-AGC-010, tRF-Gln-CTG- 005 and tRF-Leu-AAG-001 may be involved in the pathogenesis of Lupus nephritis (LN) by affecting the expression of MAPK pathway. Downregulation of tsRNA-1018, tsRNA-3045b, tsRNA-5021a and tsRNA-1020 affected the expression of MAPK pathway, thereby improving Acute lung injury (ALI) . This review comprehensively dissects tsRNA roles in MAPK signaling across cancersand other diseases, illuminating a novel avenue for translational

FAQs

What are tRNA-derived small RNAs (tsRNAs) and where do they come from?

tsRNAs are small non-coding RNAs originating from mature or precursor tRNAs (pre-tRNA), typically spanning 14 to 30 nt.

How do tsRNAs influence the MAPK signaling pathway?

tsRNAs affect MAPK signaling by targeting specific proteins within the pathway, thereby modulating MAPK pathway activity and downstream cellular outcomes.

Which cancer and non-cancer conditions does the review connect to MAPK-linked tsRNAs?

The review highlights MAPK-linked tsRNAs in gastric cancer and high-grade serous ovarian cancer, and also summarizes associations reported across several non-cancer diseases, including varicose vein risk, spinal cord injury, diabetes-related disorders, lupus-related conditions, acute lung injury, and others.

Sep 21, 2026

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