Circulating exosomal microRNA‐96 promotes cell proliferation, migration and drug resistance by targeting LMO7

• Published in: Journal of cellular and molecular medicine Vol. 21; no. 6; pp. 1228 - 1236
• Main Authors: Wu, Hao, Zhou, Jingcheng, Mei, Shanshan, Wu, Da, Mu, Zhimin, Chen, Baokun, Xie, Yuancai, Ye, Yiwang, Liu, Jixian
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2017; John Wiley and Sons Inc
• Subjects: 3' Untranslated regions; A549 Cells; Bioindicators; Biomarkers; Biomarkers, Tumor - blood; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Drug resistance; Drug Resistance, Neoplasm - genetics; exosome; Exosomes; Exosomes - genetics; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; LIM Domain Proteins - genetics; LMO7; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Metastases; MicroRNAs; MicroRNAs - blood; miRNA; miR‐96; Original; Transcription Factors - genetics; Transfection; Tumors; lung cancer; miR-96; LMO7; drug resistance; exosome
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13056

Detection and treatment of lung cancer still remain a clinical challenge. This study aims to validate exosomal microRNA‐96 (miR‐96) as a serum biomarker for lung cancer and understand the underlying mechanism in lung cancer progression. MiR‐96 expressions in normal and lung cancer patients were characterized by qPCR analysis. Changes in cell viability, migration and cisplatin resistance were monitored after incubation with isolated miR‐96‐containing exosomes, anti‐miR‐96 and anti‐miR negative control (anti‐miR‐NC) transfections. Dual‐luciferase reporter assay was used to study interaction between miR‐96 and LIM‐domain only protein 7 (LMO7). Changes induced by miR‐96 transfection and LMO7 overexpression were also evaluated. MiR‐96 expression was positively correlated with high‐grade and metastatic lung cancers. While anti‐miR‐96 transfection exhibited a tumour‐suppressing function, exosomes isolated from H1299 enhanced cell viability, migration and cisplatin resistance. Potential miR‐96 binding sites were found within the 3′‐UTR of wild‐type LMO7 gene, but not of mutant LMO7 gene. LMO7 expression was inversely correlated with lung cancer grades, and LMO7 overexpression reversed promoting effect of miR‐96. We have identified exosomal miR‐96 as a serum biomarker of malignant lung cancer. MiR‐96 promotes lung cancer progression by targeting LMO7. The miR‐96‐LMO7 axis may be a therapeutic target for lung cancer patients, and new diagnostic or therapeutic strategies could be developed by targeting the miR‐96‐LMO7 axis.