Role of exosomal microRNAs in cancer therapy and drug resistance mechanisms: focus on hepatocellular carcinoma

Abstract

Extracellular vesicles (EVs), defined as intercellular messengers that carry their cargos between cells, are involved in several physiological and pathological processes. These small membranous vesicles are released by most cells and contain biological molecules, including nucleic acids, proteins and lipids, which can modulate signaling pathways of nearby or distant recipient cells. Exosomes, one the most characterized classes of EVs, include, among others, microRNAs (miRNAs), small non-coding RNAs able to regulate the expression of several genes at post-transcriptional level. In cancer, exosomal miRNAs have been shown to influence tumor behavior and reshape tumor microenvironment. Furthermore, their possible involvement in drug resistance mechanisms has become evident in recent years. Hepatocellular carcinoma (HCC) is the major type of liver cancer, accounting for 75-85% of all liver tumors. Although the improvement in HCC treatment approaches, low therapeutic efficacy in patients with intermediate-advanced HCC is mainly related to the development of tumor metastases, high risk of recurrence and drug resistance. Exosomes have been shown to be involved in pathogenesis and progression of HCC, as well as in drug resistance, by regulating processes such as cell proliferation, epithelial-mesenchymal transition and immune response. Herein, we summarize the current knowledge about the involvement of exosomal miRNAs in HCC therapy, highlighting their role as modulators of therapeutic response, particularly chemotherapy and immunotherapy, as well as possible therapeutic tools.

Ropivacaine combined with sorafenib attenuates hepatocellular carcinoma cell proliferation and metastasis by inhibiting the miR‐224/HOXD10 axis

“…Dysregulation of miRNAs is frequently observed in drug‐resistant HCC or HCC cells 27 . miR‐224 is considered an oncogenic miRNA in liver cancer and data have related that the miR‐224 is related to the growth of HCC, and degradation of miR‐224 by autophagy inhibits HCC 28 .…”

“…Combined application of Rop and Sor in clinical practice may potentially lower the dosage of Sor, reduce the occurrence of side effects and drug resistance in patients, and improve patient prognosis. These have significant clinical implications.Dysregulation of miRNAs is frequently observed in drugresistant HCC or HCC cells 27. miR-224 is considered an oncogenic miRNA in liver cancer and data have related that the miR-224 is related to the growth of HCC, and degradation of miR-224 by autophagy inhibits HCC 28.…”

Extracellular Vesicle (EVs) Associated Non-Coding RNAs in Lung Cancer and Therapeutics

“…Exploring the probable processes that reduce therapeutic effectiveness would therefore aid in developing better cancer therapies. Exosomal miRNAs had a role in EGFR-TKI resistance as well [ 151 ]. For instance, Jing et al demonstrated the transfer of exosomal miR-21 from gefitinib-resistant H827R cells to gefitinib-sensitive HCC827 cells, where it subsequently stimulated AKT signaling and resulted in gefitinib resistance [ 152 ].…”

Spotlights on extracellular vesicles in hepatocellular carcinoma diagnosis and treatment: an update review

“…It constitutes approximately 75%–85% of all liver tumors ( Siegel et al, 2023 ). Despite advancements in hepatocellular carcinoma (HCC) treatment approaches, the therapeutic response of patients with intermediate to advanced HCC remains low due to factors such as tumor recurrence, metastasis, and drug resistance, resulting in a dismal prognosis ( Wang et al, 2022 ; Zelli et al, 2022 ). Since their discovery in 1983 ( Harding et al, 1983 ), extracellular vesicles (EVs) have evolved from being perceived as mere cellular waste disposal systems to a novel mechanism of intercellular communication.…”