CircRNA_100395 Carried by Exosomes From Adipose-Derived Mesenchymal Stem Cells Inhibits the Malignant Transformation of Non-Small Cell Lung Carcinoma Through the miR-141-3p-LATS2 Axis.

Chong Zhang,Haibo Mou,Wang Lv,Jinlin Cao

doi:10.3389/fcell.2021.663147

Abstract

Objective: The specific purpose of this study is to investigate the impact exosomes from adipose-derived mesenchymal stem cell (AMSC) has on non-small cell lung carcinoma (NSCLC) and the relative applications. Methods: circ_100395, miR-141-3p, and LATS2 were expressed and detected in NSCLC and paracancerous tissues as well as NSCLC cell lines. Pearson correlation analysis, Dual-Luciferase Reporter Assay and RNA pull-down assay were used to validate their expression and interaction, respectively. After isolation and culture of AMSCs, exosomes were extracted and identified. EdU, epithelial-mesenchymal transition (EMT), and cell colony formation assay were used to distinguish the biological activity of the cells. Expression Hippo/YAP signalling pathway-related proteins were measured by western blotting. Subsequently, tumour volume and weight were confirmed based on xenograft nude mice models, Ki-67 and LATS2 expression was observed by immunohistochemistry. Results: circ_100395 was lowly expressed in NSCLC tissues or cells. The negative correlations and interactions were confirmed between circ_100395 and miR-141-3p, miR-141-3p, and LATS2. AMSC-derived exosomes with overexpression of circ_100395 (exo-circ_100395) significantly inhibited the biological activity as well as EMT of H1650 cells and Hippo/YAP signalling pathway activity. In addition, exo-circ_100395 markedly reduced tumour volume and weight as well as Ki-67 and LASP1 expression in vivo. However, overexpressed miR-141-3p or knocked down LATS2 alleviated the above effects. Conclusion: Exo-circ_100395 can increase LATS2 expression by sponging miR-141-3p to regulate Hippo/YAP signalling pathway, thereby inhibiting NSCLC malignant transformation.

Highlights

One of the leading risk factors causing death in cancer patients within industrial countries is non-small cell lung carcinoma (NSCLC)
Culture and Treatment of Mesenchymal Stem Cells That Are Adipose-Derived Human subcutaneous adipose tissue was acquired from patients undergoing abdominal liposuction in The First Affiliated Hospital, Zhejiang University School of Medicine
H1650 cells were used for subsequent experiments

Summary

Introduction

One of the leading risk factors causing death in cancer patients within industrial countries is non-small cell lung carcinoma (NSCLC). NSCLC accounts for about 85% of all existing lung cancers with a below 15% survival rate (Bunn et al, 2003; Siegel et al, 2017). Therapeutic effects on NSCLC is very limited. NSCLC patients cannot be cured by these methods and the prognosis is poor (Jemal et al, 2011). Inhibiting angiogenesis as a treatment for NSCLC has existed and utilised in clinical testing for several years (Abéngozar et al, 2012). The transmission of cytotoxic drugs to lesions can be weakened by angiogenesis inhibitors, resulting in affected therapeutic effects of the relating anti-tumour drugs (Van der Veldt et al, 2012). Thereby, finding new treatments for NSCLC is urgently needed

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Conclusion