Exosomal microRNAs and long noncoding RNAs: Novel mediators of drug resistance in lung cancer

Abstract

Lung cancer therapeutic resistance, especially chemoresistance, is a key issue in the management of this malignancy. Despite the development of novel molecularly targeted drugs to promote therapeutic efficacy, 5‐year survival of lung cancer patients is still dismal. Molecular studies through the recent years have fortunately presented multiple genes and signaling pathways, which contribute to lung cancer chemoresistance, providing a better perception of the biology of tumor cells, as well as the molecular mechanisms involved in their resistance to chemotherapeutic agents. Among those mechanisms, transfer of extracellular vesicles, such as exosomes, between cancer cells and the surrounding noncancerous ones is considered as an emerging route. Exosomes can desirably function as signaling vesicles to transmit multiple molecules from normal cells to cancer cells and their microenvironment, or vice versa. Using this ability, exosomes may affect the cancer cells' chemoresistance/chemosensitivity. Recently, noncoding RNAs (esp. microRNAs and long noncoding RNAs), as key molecules transferred by exosomes, have been reported to play a substantial role in the process of drug resistance, through modulation of various proteins and their corresponding genes. Accordingly, the current review principally aims to highlight exosomal micro‐ and long noncoding RNAs involved in lung cancer chemoresistance. Moreover, major molecular mechanisms, which connect corresponding RNA molecules to drug resistance, will briefly be addressed, for better clarifying of possible roles of exosomal noncoding RNAs in promoting the effectiveness of lung cancer therapy.

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms

“…In this context, exosomal ncRNAs have been shown to be correlated with various human cancers, such as BC, lung cancer, hepatocellular carcinoma (HCC), glioblastomas, and prostate cancer. ( Li et al, 2018a ; He et al, 2018 ; Hu et al, 2020a ; Movahedpour et al, 2021 ; Movahedpour et al, 2022a ; Taghvimi et al, 2022 ). For instance, in the case of HCC, exosomal ncRNAs interfere with the process of liver fibrosis and subsequent cirrhosis and consequently provoke tumorigenesis and HCC development ( Quail and Joyce, 2013 ; Bukong et al, 2014 ).…”

Emerging noncoding RNAs contained in extracellular vesicles: rising stars as biomarkers in lung cancer liquid biopsy

“…34,[42][43][44] Several reports demonstrate the key role of EVs in cancer progression, 45 premetastatic niche formation, 46 metastasis, 47,48 and drug resistance. 49,50 The potential for EVs as biomarkers in LC early detection and progression has been reported as well. EVs have been identified as good biomarkers for monitoring response to LC therapies.…”

Exosome-Derived Non-Coding RNAs in the Tumor Microenvironment of Colorectal Cancer: Possible Functions, Mechanisms and Clinical Applications

“…Abundant studies have shown that ncRNAs are significantly enriched in exosomes, which spread to the TME and remodel TME, ultimately leading to tumor metastasis, such as angiogenesis, vascular permeability, tumor immunity, tumor metabolism, drug resistance ( Figure 1 ) ( 80 – 82 ). Additionally, drug resistance is closely linked to TME, exosomal ncRNAs play key roles in tumor cell adaptation to the TME and drug resistance ( 83 ). Based on the current studies, we discussed the role and mechanism of exosomal ncRNAs in TME of CRC in this section ( Figure 2 ).…”