MicroRNAs and RNA-Binding Protein-Based Regulation of Bone Metastasis from Hepatobiliary Cancers and Potential Therapeutic Strategies

Sep 21, 2026

Hepatobiliary cancers such as hepatocellular carcinoma and cholangiocarcinoma are among the most lethal malignancies, and although bone metastases are uncommon, they are highly aggressive with poor outcomes. This review summarizes RNA-based molecular mechanisms driving bone metastasis, emphasizing microRNAs and RNA-binding proteins and their abnormal expression in hepatobiliary tumors. By perturbing bone homeostasis, these pathways support tumor cell migration and survival in the bone microenvironment. It also outlines therapeutic strategies targeting miRNA- and RBP-related routes and stresses the need for diagnostic and prognostic biomarkers and effective treatments.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Abstract

Introduction

Hepatobiliary cancers and causes

Treatment landscape

Metastasis patterns and prognosis

Bone metastasis characteristics

Review MicroRNAs and RNA-Binding Protein-Based Regulation of Bone Metastasis from Hepatobiliary Cancers and Potential Therapeutic Strategies Sharmila Fagoonee 1, * and Ralf Weiskirchen 2, * Citation: Fagoonee, S.; Weiskirchen, R. MicroRNAs and RNA-Binding Protein-Based Regulation of Bone Metastasis from Hepatobiliary Cancers and Potential Therapeutic Strategies. Cells 2024, 13, 1935 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells13231935 Academic Editors: Maria Teresa Valenti and Roberta Zerlotin Received: 28 October 2024 Revised: 15 November 2024 Accepted: 20 November 2024 Published: 21 November 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Institute of Biostructure and Bioimaging (CNR), Molecular Biotechnology Center “Guido Tarone”, 10126 Turin, Italy 2 Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany * Correspondence: sharmila.fagoonee@unito.it (S.F.); rweiskirchen@ukaachen.de (R.W.) Abstract: Hepatobiliary cancers, such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are among the deadliest malignancies worldwide, leading to a significant number of cancerrelated deaths. While bone metastases from these cancers are rare, they are highly aggressive and linked to poor prognosis. This review focuses on RNA-based molecular mechanisms that contribute to bone metastasis from hepatobiliary cancers. Specifically, the role of two key factors, microRNAs (miRNAs) and RNA-binding proteins (RBPs), which have not been extensively studied in the context of HCC and CCA, is discussed. These molecules often exhibit abnormal expression in hepatobiliary tumors, influencing cancer cell spread and metastasis by disrupting bone homeostasis, thereby aiding tumor cell migration and survival in the bone microenvironment. This review also discusses potential therapeutic strategies targeting these RNA-based pathways to reduce bone metastasis and improve patient outcomes. Further research is crucial for developing effective miRNA-and RBP-based diagnostic and prognostic biomarkers and treatments to prevent bone metastases in hepatobiliary cancers. Keywords: hepatocellular carcinoma; cholangiocarcinoma; bone metastases; extracellular vesicles; RNA-binding proteins; microRNAs; therapy; biomarkers 1. Introduction Hepatobiliary cancers, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), gall bladder cancer (GC), extrahepatic cholangiocarcinoma (eCCA), and ampullary cancer, are among the deadliest malignancies and account for approximately 13% of cancer-related deaths worldwide [1] . HCC develops in chronic liver inflammatory conditions, such as viral infections like hepatitis B virus (HBV) or hepatitis C virus (HCV), metabolic dysfunction-associated steatohepatitis (MASH), alcohol consumption, tobacco smoking, primary biliary cholangitis, and hemochromatosis, with the molecular pathogenesis varying based on the genotoxic insults and etiology [2,3] . Unresolved fibrosis from any etiology leading to cirrhotic changes is the primary risk factor for HCC. CCA arises against a background of biliary inflammation and fibrosis, originating from biliary epithelial cells or cholangiocytes lining the intrahepatic bile duct [4] . Among biliary tract cancers, iCCA (discussed in this review as representative of CCA) can also develop from chronic viral infections (HBV or HCV) or MASH, as well as biliary tract disorders, like choledochal cyst, cholelithiasis, primary sclerosing cholangitis (PSC), environmental toxins, and cirrhosis

FAQs

Why are bone metastases important in hepatobiliary cancers?

Bone metastases are rare but highly aggressive and associated with poor prognosis. The review links them to increased morbidity and mortality in advanced disease stages.

What roles do microRNAs and RNA-binding proteins play in bone metastasis?

MicroRNAs and RNA-binding proteins show abnormal expression in hepatobiliary tumors. They influence cancer spread by disrupting bone homeostasis and promoting tumor cell migration and survival within the bone microenvironment.

What therapeutic directions are discussed for reducing bone metastasis?

The review discusses potential therapeutic strategies that target miRNA- and RBP-based RNA pathways. It also highlights the need to develop effective diagnostic and prognostic biomarkers and treatments.

Sep 21, 2026

Uploaded by Clementine