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.

SUBMITTER: Wu H 

PROVIDER: S-EPMC5431139 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature