MicroRNAs contribute to ATP-binding cassette transporter- and autophagy-mediated chemoresistance in hepatocellular carcinoma

ESPELT, MARÍA V; BACIGALUPO, MARÍA L; CARABIAS, PABLO; TRONCOSO, MARÍA F

World Journal of Hepatology

Baishideng Publishing Group Inc

Año: 2019 vol. 11 p. 344 - 358

1948-5182

Hepatocellular carcinoma (HCC) has an elevated mortality rate, largely becauseof high recurrence and metastasis. Additionally, the main obstacle duringtreatment of HCC is that patients usually develop resistance to chemotherapy.Cancer drug resistance involves many different mechanisms, includingalterations in drug metabolism and processing, impairment of the apoptoticmachine, activation of cell survival signaling, decreased drug sensitivity andautophagy, among others. Nowadays, miRNAs are emerging as masterregulators of normal physiology- and tumor-related gene expression. In HCC,aberrant expression of many miRNAs leads to chemoresistance. Herein, weparticularly analyzed miRNA impact on HCC resistance to drug therapy. CertainmiRNAs target ABC (ATP-binding cassette) transporter genes. As most of thesemiRNAs are downregulated in HCC, transporter levels increase and intracellulardrug accumulation decrease, turning cells less sensitive to death. Others miRNAstarget autophagy-related gene expression, inhibiting autophagy and acting astumor suppressors. Nevertheless, due to its downregulation in HCC, thesemiRNAs do not inhibit autophagy or tumor growth and, resistance is favored.Concluding, modulation of ABC transporter and/or autophagy-related geneexpression or function by miRNAs could be determinant for HCC cell survivalunder chemotherapeutic drug treatment. Undoubtedly, more insights on thebiological processes, signaling pathways and/or molecular mechanismsregulated by miRNAs are needed. Anyway, miRNA-based therapy together withconventional chemotherapeutic drugs has a great future in cancer therapy.