Bone marrow mesenchymal stem cells-derived exosomal microRNA-193a reduces cisplatin resistance of non-small cell lung cancer cells via targeting LRRC1

Abstract

Exosomes are small endogenous membrane vesicles that can mediate cell communication by transferring genetic materials. Based on that, exosomes have always been discussed as a cargo carrier for microRNA (miRNA) transportation. Accumulating data have reported the inhibitory effects of microRNA-193a (miR-193a) on non-small cell lung cancer (NSCLC) cell progression. However, the mechanisms of miR-193a delivery to cancer cells and miR-193a in exosomes have not been explored clearly in NSCLC. Given that, this work aims to decode exosomal miR-193a in cisplatin (DDP) resistance of NSCLC cells. A549 and H1299 cell lines were screened out and their parent cells and drug-resistant cells were co-cultured with human bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exo) that had been transfected with miR-193a mimic or si-LRRC1 to detect the colony formation, migration, apoptosis, invasion and proliferation of NSCLC cells. In vivo experiment was conducted to verify the in vitro results. BMSC-Exo with upregulated miR-193a and downregulated LRRC1 suppressed colony formation, invasion, proliferation and migration as well as advanced apoptosis of NSCLC parent cells and drug-resistant cells. BMSC-Exo combined with upregulated miR-193a reduced tumor volume and weight in mice with NSCLC. Functional studies report that BMSC-Exo shuffle miR-193a to suppress the colony formation, invasion, migration, and proliferation as well as advance apoptosis of NSCLC DDP-resistant cells via downregulating LRRC1.

Integrative analysis of exosomal microRNA-149-5p in lung adenocarcinoma

“…Elsewhere, exosomal miR-382-5p released from oral squamous cell carcinoma cells stimulated tumor cells migration and invasion ability [ 20 ]. In non-small cell lung cancer, BMMSC-derived exosomes transferred miR-193a to induce cisplatin resistance via suppressing LRRC1 [ 21 ]. In previous studies, miR-149-5p was found to be highly expressed in lung adenocarcinoma cells and influenced tumor cells metastasis [ 22 , 23 ].…”

Cell-derived biomimetic nanocarriers for targeted cancer therapy: cell membranes and extracellular vesicles

“…The membrane protein enables PLT-PPy-Dox to evade the attack of immune cells and precisely target the tumor, laser irradiation causes PPy to produce hyperthermia and ablate the tumor cells, and Dox is also released from the NPs to effectively destroy the tumor. In addition, after three consecutive PTT cycles, the temperature of the tumor tissue increases, and then the tumor cells are burned; Due to PLTM recognize and accumulate in the injured site, PLT-PPy-Dox is more gathered in the tumor site, which promotes the efficiency of PTT (Wu et al, 2020 ). Therefore, the strategy of using biomimetic materials and combination therapy in the treatment of tumors has significant effects and promising prospects.…”

“…Ying et al transfected miR-193a into BM-MSCs-EXOs to target focal adhesion kinase in colon cancer, which downregulated the expression of focal adhesion kinase and inhibited the invasion, migration and proliferation of colon cancer cells (François et al, 2019 ; Ying et al, 2020 ). In another study, BM-MSCs-EXOs carrying miR-193A promoted apoptosis in drug-resistant lung cancer cells by downregulating LRRC1 (Wu et al, 2020 ). However, few studies have examined the transport RNA of BM-MSCs-EXOs to tumor stem cells, which creates new and feasible carriers for tumor drug delivery and has the value of further exploration.…”

The Significance of Exosomal RNAs in the Development, Diagnosis, and Treatment of Gastric Cancer

“…Besides, chemotherapy and radiation therapy could also directly affect exosome biogenesis and the content of exosomes with potential implications on therapy outcome. It should be noted that the function of exosomal RNA in drug resistance is complicated and some scholars claim that exosomal RNAs may also play a role in reducing drug resistance [ 88 ]. Apart from chemoresistance, exosomes are also found to be of great value in determining outcomes in radiation therapy and some studies suggested that exosomes may induce the radiation-induced bystander effect (RIBE) [ 89 ].…”