The interplay between noncoding RNAs and drug resistance in hepatocellular carcinoma: the big impact of little things

Sep 24, 2026

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Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major cause of cancer-related death, hindered by lack of early diagnosis and frequent recurrence after resection. Systemic therapy is crucial for advanced disease, yet conventional molecular drugs often face adverse reactions, limited sensitivity, and drug resistance. Noncoding RNAs (miRNAs, lncRNAs, circRNAs) are established regulators of cancer development and progression. This review consolidates evidence linking ncRNAs to drug-resistance control in HCC and evaluates clinical opportunities to overcome resistance barriers, including targeted therapy and chemotherapy strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Abstract

Background

Disease burden and treatment landscape

Therapeutic strategies and drug classes

Drug resistance: intrinsic and acquired mechanisms

Fang et al. Journal of Translational Medicine (2023) 21:369 [https://doi.org/10.1186/s12967-023-04238-9](https://doi.org/10.1186/s12967-023-04238-9) Journal of Translational Medicine REVIEW Open Access The interplay between noncoding RNAs and drug resistance in hepatocellular carcinoma: the big impact of little things Yuan Fang1†, XiaoLi Zhang2†, HanFei Huang1* and Zhong Zeng1* Abstract Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death in people, and a common primary liver cancer. Lacking early diagnosis and a high recurrence rate after surgical resection, systemic treatment is still an important treatment method for advanced HCC. Different drugs have distinct curative effects, side effects and drug resistance due to different properties. At present, conventional molecular drugs for HCC have displayed some limitations, such as adverse drug reactions, insensitivity to some medicines, and drug resistance. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), have been well documented to be involved in the occurrence and progression of cancer. Novel biomarkers and therapeutic targets, as well as research into the molecular basis of drug resistance, are urgently needed for the management of HCC. We review current research on ncRNAs and consolidate the known roles regulating drug resistance in HCC and examine the potential clinical applications of ncRNAs in overcoming drug resistance barriers in HCC based on targeted therapy, cell cycle non-specific chemotherapy and cell cycle specific chemotherapy. Keywords Hepatocellular carcinoma, Noncoding RNAs, Drug resistance, Targeted therapy, Immune therapy Background Hepatocellular carcinoma (HCC) accounts for around 90% of primary liver cancer cases and is associated with high mortality rates, as the sixth most prevalent cancer worldwide [1]. HCC is commonly associated with HBVor HCV infection, alcohol abuse, or nonalcoholic fatty †Yuan Fang and XiaoLi Zhang contributed equally to this work. *Correspondence: HanFei Huang [huanghanfei@kmmu.edu.cn](huanghanfei@kmmu.edu.cn)[ ](huanghanfei@kmmu.edu.cn)Zhong Zeng [zengzhong@kmmu.edu.cn](zengzhong@kmmu.edu.cn) 1 Organ Transplantation Center, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming 650032, Yunnan, People’s Republic of China 2 Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China liver disease (NAFLD) [2]. There are various therapeutic methods to treat pre-HCC, such as surgical resection, radiofrequency ablation, absolute ethanol injection, and chemoembolization [3]. Hepatic resection remains the first choice of treatment, even if it is associated with 70% of tumor recurrence and metastasis at 5 years [4]. Furthermore, systemic therapy is considered as the last line of defense for patients with postoperative recurrence, malignant vascular invasion, and extrahepatic spread, and for patients who are not application for operation [5]. The mainstay of cancer treatment is comprised of chemotherapy, immunotherapy, and targeted therapy [6]. Commonly employed therapeutic regimens for cancer treatment include drugs such as sorafenib (SOR), lenvatinib, regorafenib, 5-fluorouracil (5-FU), adriamycin (ADM), platinum-based chemotherapy, camptothecin, and gemcitabine. Meanwhile, Atezolizumab +Bevacizumab therapy, cabozantinib therapy © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative C

FAQs

Which types of noncoding RNAs are discussed as regulators of drug resistance in HCC?

The document focuses on noncoding RNAs including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). It summarizes how they contribute to regulating drug resistance in hepatocellular carcinoma.

Sep 24, 2026

Uploaded by Ophelia