Exosomal miR-141 is a Biomarker for Lung Cancer Angiogenesis and Malignant Progression

Abstract

Background: Early diagnosis of lung cancer helps to extend the patients survival time. Our previous study demonstrated that tumor-derived exosomal microRNA-141 (miR-141) promotes lung cancer angiogenesis and malignant progression by targeting the gene transcript for growth arrest-specific homeobox (GAX). Here, we evaluated miR-141s prognosis value to lung cancer diagnosis. Methods: MiR-141 was steady overexpressed in A549 cell by lentivirus vector. The GAX was expressed in miR-141+ cells by pcDNA 3.1 (+) plasmid. The protein expression levels were assessed using western blot analysis. The functional significance of miR-141 and GAX was further investigated in vivo models. MiR-141 level in cells and serum were detected by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Results: The overexpression of miR-141 has been shown to enhance cellular proliferation and migration. Overexpression of miR-141 accompanied with rescue overexpression of GAX in cells could restore cell proliferation and migration to control. We induced constitutive overexpression of miR-141 in the A549 cell line (A549-miR-141) and found that the tumor growth rate of A549-miR-141 was faster than that of the control group in a nude xenograft mouse model. The tumors in the A549-miR-141 group were significantly enriched in blood vessels relative to the control group. Correlation of clinical information and miR-141 expression levels within the serum exosomes from 98 lung cancer patients showed that serum miR-141 levels were unrelated to gender, age, operation, chemotherapy, or radiotherapy. However, the mRNA level of miR-141 was correlated with clinical stage and lymph node metastasis (p < 0.001). In addition, there was strong correlation between overall survival and the level of miR-141, with longer overall survival in patients with lower miR-141 expression level. Conclusions: Our study suggests that exosomal miR-141 derived from lung cancer cells promotes angiogenesis and facilitates malignant progression. The expression level of serum exosome miR-141 exhibits a significant correlation with the clinical stage and lymph node metastasis, thereby offering a novel prognostic marker and potential therapeutic target for lung cancer management.