Objective: To investigate the role of miR-381 in the progression of lung adenocarcinoma (LA) and its underlying mechanism.
Patients and methods: A total of 54 pairs of LA tissues and para-carcinoma tissues were obtained from May 2015 to April 2017 in our hospital. Four human LA cell lines (A549, SPC-A1, H1299, and PC-9) and one normal human pulmonary epithelial cell line BEAS-2B were obtained and cultured. The protein and mRNA expression levels were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Additionally, cell proliferation assays and cell migration and invasion assays were used. Furthermore, tumor xenograft model in nude mice was made in this study.
Results: miR-381 was notably downregulated in LA tissues. Moreover, low miR-381 expression was confirmed to be strongly correlated with poor prognosis and aggressive clinicopathological characteristics of LA patients. Exogenous miR-381 overexpression was found to notably restrict LA cell proliferation, migration, and invasion; additionally, miR-381 overexpression could significantly reduce tumor growth in vivo. Mechanistically, LMO3 was determined as a novel direct target for miR-381 in LA cells. In clinical LA tissues, the LMO3 expressions were clearly overexpressed. Furthermore, miR-381 overexpression affected the PI3K/Akt pathway and EMT in LA.
Conclusions: MiR-381 played key roles in LA progression, partially via directly targeting LMO3 and regulating the PI3K/Akt signaling pathway and EMT. Thus, the miR-381/ LMO3 axis has clinical significance in the therapy of patients with LA.