Heterogeneous nuclear ribonucleoprotein K in cancer biology and its therapeutic applications - Review

Sep 22, 2026

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional RNA-binding protein whose K-homology domain is highly conserved and enables RNA binding. hnRNPK interacts with chromatin and RNA, coordinating signaling integration with regulation of gene expression, RNA processing, cell cycle control, and apoptosis. In multiple tumors, hnRNPK shows abnormal expression and can act as oncogene or tumor suppressor depending on cellular context and post-translational modifications. The review details its roles in migration, angiogenesis, and chemoresistance via long non-coding RNAs and key signaling pathways, emphasizing clinical biomarker and therapeutic potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

hnRNP family

hnRNPK structure

hnRNPK function

Biological function of hnRNPK in tumors

Expression and prognostic value of hnRNPK in malignant tumors

Conclusion

MOLECULAR MEDICINE REPORTS 33: 144, 2026 Heterogeneous nuclear ribonucleoprotein K in cancer biology and its therapeutic applications (Review) YIYU QIN and YANG ZHOU School of Medicine, Jiangsu Medical College, Yancheng, Jiangsu 224000, P.R. China Received June 27, 2025; Accepted December 3, 2025 DOI: 10. 3892/mmr.2026.13854 Abstract. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional protein belonging to the hetero‑ geneous nuclear ribonucleoprotein family. The K‑homology domain is the most evolutionarily conserved feature of hnRNPK and is responsible for RNA‑binding. hnRNPK interacts with both chromatin and RNA in numerous species. Initially characterized as an RNA‑binding protein, hnRNPK functions as a structural protein, integrating a number of signaling pathways and participating in gene expression regulation, RNA processing, cell cycle control and apoptosis. hnRNPK exhibits aberrant expression in numerous tumors, functioning paradoxically as either an oncogene or tumor suppressor depending on cellular context, expression levels and post‑translational modifications. Recent advancements have outlined the involvement of hnRNPK in tumor cell migration, angiogenesis and chemoresistance through interactions with long non‑coding RNAs and the regulation of key signaling pathways. The present review summarizes current knowledge regarding the structure, function and clinical importance of the hnRNPK in cancer, highlighting its potential as both abiomarker and therapeutic target. Contents 1. Introduction 2. hnRNP family 3. hnRNPK structure 4. hnRNPK function 5. Biological function of hnRNPK in tumors 6. Expression and prognostic value of hnRNPK in malignant tumors 7. Conclusion Correspondence to: Dr Yiyu Qin, School of Medicine, Jiangsu Medical College, 283 Jiefang South Road, Yancheng, Jiangsu 224000, P.R. China E‑mail: [qinyiyu128@163.com](qinyiyu128@163.com) Key words: heterogeneous nuclear ribonucleoprotein K, malignant tumor, RNA binding protein, oncogenesis 1. Introduction Cancer remains one of the leading causes of mortality world‑ wide and involves the dysregulation of molecular pathways that control fundamental cellular processes, including proliferation, apoptosis, migration and invasion . The regulation of gene expression serves a key role in maintaining cellular homeo‑ stasis and preventing malignant transformation. Accumulating evidence has highlighted the key role that RNA‑binding proteins (RBPs) serve in orchestrating these regulatory networks, particularly in cancer development and progression (1). Among RBPs, heterogeneous nuclear ribonucleoproteins (hnRNPs) represent a particularly important subfamily that governs RNA metabolism, including transcription, splicing, stability and translation. The hnRNP family comprises >20 members, each with distinct structural domains and functional capabilities. These proteins exhibit notable versatility in shuttling between the nuclear and cytoplasmic compartments and participating in diverse cellular processes, ranging from chromatin remodeling to signal transduction. Evidence suggests that the dysregulation of hnRNP proteins markedly contributes to oncogenesis and tumor progression in a number of cancer types (2) . hnRNPKhas emerged as a promising member of this family owing to its multifaceted roles and aberrant expression patterns in numerous malignancies, including gastric cancer, colorectal cancer, hepa‑ tocellular carcinoma, lung cancer, acute myeloid leukemia and bladder cancer (3). Characterized by its signature K‑homology (KH) domains, hnRNPK functions as a multifunctional regu‑ lator that interfaces with DNA, RNA and protein components. The ability of hnRNPK to modulate gene expression at multiple levels serves as a key hub in the molecular networks governing cell fate decisions. With this, the dynamic subcellular localiza‑ tion of hnRNPK underscores its potential as a therapeutic target and biomarker. Despite

FAQs

What roles does hnRNPK play in cancer biology?

hnRNPK regulates gene expression and RNA processing, coordinates signaling pathways, and influences cell cycle control and apoptosis. Aberrant hnRNPK expression is linked to tumor behaviors including migration, angiogenesis, and chemoresistance.

How does hnRNPK recognize RNA at the molecular level?

The K-homology (KH) domain is evolutionarily conserved and is responsible for RNA binding. hnRNPK contains signature KH domains and interacts with RNA and DNA components.

Why can hnRNPK act as both an oncogene and a tumor suppressor?

Its effect depends on cellular context, expression levels, and post-translational modifications. The review describes this dual nature as a key unresolved aspect and a driver for future therapeutic research.

Sep 22, 2026

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