The Role of miRNA-21 in the Metastasis of Hepatocellular Carcinoma as a Therapeutic Target

Sep 22, 2026

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Hepatocellular carcinoma (HCC) is a major global health challenge and the most common primary liver cancer, with high mortality driven by invasion and metastasis. This review analyzes microRNA-21 (miR-21), a noncoding RNA implicated in oncogenic functions, and explains how it promotes HCC dissemination through key pathway interactions, including PTEN/PI3K/AKT, PDCD4/AP-1, RECK/MMP, and TIMP-3. By suppressing tumor suppressors, miR-21 facilitates EMT, invasion, and metastatic behavior, supporting its value as a potential therapeutic target.

LanguageEnglish

CategoryHealthcare

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Pages13

Reading Time33 min

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Abstract

Introduction

Cancer and metastasis mechanisms

Types and burden of primary liver cancer

Clinical symptoms and risk factors for HCC

The Role of miRNA-21 in the Metastasis of Hepatocellular Carcinoma as a Therapeutic Target Mahdi Alaee1, Meysam Moulaee2, Kimia Taebi3,4, Ahoura Haghi5, Maryam Hormozi2, Mehdi Azad6 1Shahid Rajaee Hospital, Qazvin University of Medical Sciences, Qazvin, Iran 2Department of Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran 3Student Research Committee, Qazvin University of Medical Sciences, Qazvin, Iran 4USERN Office, Qazvin University of Medical Sciences, Qazvin, Iran 5Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Italy 6Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences , Qazvin, Iran Corresponding Author: Mehdi Azad; Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran E-mail: [haematologicca@gmail.com](haematologicca@gmail.com) Received: 23, Jan, 2025 Accepted: 01, Dec, 2025 ABSTRACT Hepatocellular carcinoma (HCC) is a crucial health concern worldwide, representing a leading cause of cancerrelated mortality and the most common form of primary liver cancer. The aggressive nature of HCC is mainly due to its high tendency for invasion and metastasis, processes regulated by a complex network of genetic and molecular pathways. Among the critical regulators of these processes is microRNA-21 (miR-21), a small noncoding RNA that implicated in various oncogenic activities. This review provides a comprehensive analysis of the role of miR-21 in promoting HCC metastasis, with a particular focus on its interaction with key signaling pathways, including the PTEN/PI3K/AKT, PDCD4/AP-1, RECK/MMP, and TIMP-3 axes. By targeting tumor suppressors, miR-21 facilitates epithelial-to-mesenchymal transition (EMT), invasion, and metastasis of HCC cells. Understanding the molecular mechanisms regulated by miR-21 not only sheds light on the pathogenesis of HCC but also highlights potential therapeutic targets for combating this aggressive cancer. Keywords: Hepatocellular carcinoma; Cancer; Epigenetics; miR-21 INTRODUCTION Cancer is a collection of illnesses distinguished by the unregulated proliferation and division of abnormal cells with the capability of invading surrounding tissues and spreading via the lymphatic system and bloodstream to other body organs, a process known as metastasis1. This uncontrolled growth arises when cells bypass the normal regulatory mechanisms that govern cell division and death, leading to the formation of tumors. Genetic mutations and epigenetic alterations often transform normal cells into cancerous cells. These changes can result from various factors, including environmental carcinogens, radiation, and viral infections2-4. Several types of primary liver cancer exist, such as intrahepatic cholangiocarcinoma, hepatocellular carcinoma, hepatoblastoma, and fibrolamellar carcinoma, depending on the cancer originates5-8. HCC is the most common liver cancer caused by genetic changes in liver cells (hepatocytes) . In 2018, it accounted for the third-highest number of cancerrelated deaths globally, with over 780,000 fatalities recorded. Annually, around 800,000 new HCC cases are diagnosed 9. One of the main characteristics of this disease is its high rate of progression compared to other cancers, while its survival rate remains exceptionally poor10, 11. Hepatocellular carcinoma is characterized by three types of clinical symptoms, which can occur in 90 to 95 percent of people with the disease: upper right quadrant abdominal pain, palpable abdominal mass, and weight loss. Hepatomegaly (liver enlargement) and abnormalities in liver consistency are also evident. Other common symptoms include weakness, fatigue, indigestion, anorexia, shortness of breath, vomiting, splenomegaly (enlarged spleen), fever, and jaundice. In the advanced and terminal stages, patients typically present with ascites

FAQs

What role does miR-21 play in HCC metastasis?

miR-21 promotes HCC metastasis by targeting tumor suppressors and facilitating EMT, invasion, and metastatic progression.

Which signaling pathways are highlighted as miR-21-related in the review?

The review focuses on interactions involving PTEN/PI3K/AKT, PDCD4/AP-1, RECK/MMP, and TIMP-3 axes.

What factors are described as risk factors for hepatocellular carcinoma?

The text mentions chronic HBV and HCV infection, alcohol consumption, aflatoxin B1 exposure, NAFLD, obesity, and dietary and diabetes-related links.

Sep 22, 2026

Uploaded by Mabel