title: Circulating exosomal microRNA-96 promotes cell proliferation, migration and drug resistance by targeting LMO7.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Mei
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Da
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Mu
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Baokun
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Yuancai
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Yiwang
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Jixian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000072283:A549 Cells; D014408:Biomarkers, Tumor / Q000097:blood*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D055354:Exosomes / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D060588:LIM Domain Proteins; C116184:LMO7 protein, human; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D002945:Cisplatin
keywords: LMO7; drug resistance; exosome; lung cancer; miR-96