MiR-26a-5p potentiates metastasis of human lung cancer cells by regulating ITGβ8- JAK2/STAT3 axis

Highlights: • 90% of lung cancer patients die of metastasis. • miR-26a-5p enhances metastasis potential of lung cancer both in vitro and in vivo. • ITGβ8 is identified as a novel target of miR-26a-5p. • miR-26a-5p enhances lung cancer cell metastasis via activation of JAK2/STAT3 pathway. 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 (ITGβ8) as a novel target of miR-26a, and ITGβ8 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 ITGβ8 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 ITGβ8. 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.