Biochemical and Biophysical Research Communications, Vol.501, No.2, 494-500, 2018
MiR-26a-5p potentiates metastasis of human lung cancer cells by regulating ITG beta 8-JAK2/STAT3 axis
Most lung cancer patients die of metastasis. Recent studies have indicated that dysregulated microRNAs (miRNAs) are involved not only in tumorigenesis, but also in metastasis. In the present study, we found that over-expression of miR-26a-5p potentiated the migration and invasion of lung cancer cells evidenced by wound healing assay and transwell assay, and metastasis-related genes MMP-9 and CD44 were up-regulated. We identified integrin-beta8 (ITG beta 8) as a novel target of miR-26a, and ITG beta 8 expression was negatively correlated with miR-26a-5p expression in lung cancer specimens. Mechanism study showed that miR-26a-5p enhanced lung cancer cell metastasis via activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, and ITG beta 8 mediated the activation of JAK2/STAT3 pathway by miR-26a-5p. By using in vivo imaging technology, we found that miR-26a-5p enhanced both tumor growth and metastasis in vivo; and activated JAK2/STAT3 pathway. Taken together, our results demonstrated that miR-26a-5p potentiated lung cancer cell metastasis via JAK2/STAT3 pathway by targeting ITG beta 8. This finding provides insights into the mechanism underlying miRNAs regulation on lung cancer metastasis; and suggests miR-26a-5p as a therapeutic target for lung cancer treatment. (C) 2018 Elsevier Inc. All rights reserved.