MicroRNAs Modulate Drug Resistance-Related Mechanisms in Hepatocellular Carcinoma - PubMed (original) (raw)

Review

Yuehui Liang et al. Front Oncol. 2020.

Abstract

Primary liver cancer [hepatocellular carcinoma (HCC)] is one of the most common malignant tumors worldwide, causing serious health threats because of its high morbidity and mortality, rapid growth, and strong invasiveness. Patients with HCC frequently develop resistance to the current chemotherapeutic drugs, and this is largely attributed to the high-level heterogeneity of the tumor tissue. MicroRNAs (miRNAs) are a group of master regulators for multiple physiological and pathological processes and play important roles in the tumorigenesis. More recent studies have indicated that miRNAs also play a non-negligible role in the development of drug resistance in liver cancer. In this review, we summarize the data from the latest studies on the mechanisms of drug resistance in liver cancer, including autophagy, membrane transporters, epithelial-mesenchymal transitions (EMTs), tumor microenvironment, and genes and proteins that are associated with apoptosis. The data herein will provide valuable information for the development of novel approaches to tackle drug resistance in the management of liver cancer.

Keywords: autophagy; drug resistance; hepatocellular carcinoma; microRNAs; tumor microenvironment.

Copyright © 2020 Liang, Liang, Qiao and Xiao.

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Figures

Figure 1

Figure 1

Role of microRNAs (miRNAs) in the regulation of autophagy-related drug resistance. MiRNAs exert important roles in drug resistance through positive or negative regulation of key molecules or pathways of autophagy.

Figure 2

Figure 2

A schematic diagram illustrating the mechanisms of how microRNAs (miRNAs) regulate membrane transporter in the development of drug resistance. MiRNAs may affect the entrance of chemotherapy drugs into cells by negatively regulating membrane transport receptor.

Figure 3

Figure 3

Role of microRNAs (miRNA)-regulated epithelial–mesenchymal transition (EMT) in the development of resistance. Epithelial cells are more sensitive to chemotherapeutic drugs, whereas mesenchymal cells are resistant to the drugs and more aggressive. MiRNAs mainly affect drug resistance through negative regulation of key molecules in the EMT process.

Figure 4

Figure 4

Role of cancer stem cells (CSCs), hypoxia, and the Warburg effect regulated by MICRORNAS (miRNAs) in the development of drug resistance. MiRNAs mainly affect drug resistance through negative regulation of key molecules in the above process.

Figure 5

Figure 5

Key mechanisms related to drug resistance in hepatoma cells. MicroRNAs (miRNAs) can affect the outcome of chemotherapy, mainly acting on key molecules or signaling pathways related to the above mechanisms.

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