JMJD3 enhances invasiveness and migratory capacity of non-small cell lung cancer cell via activating EMT signaling pathway

OBJECTIVE: This study aimed to explore the expression of JMJD3 in non-small cell lung cancer (NSCLC) and to further study its association with clinical features and prognosis of patients. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the level of JMJD3 in 46 pairs of NSCLC tissues and para-cancerous specimens. The relationship between JMJD3 level and clinical features of NSCLC and patients' prognosis was analyzed. And JMJD3 expression in NSCLC cells was further verified by qRT-PCR. In addition, JMJD3 knockdown model was constructed using siRNA in cell lines including A549 and SPC-A1, and the effect of JMJD3 on the biological function of NSCLC cells was analyzed by cell counting kit-8 (CCK-8) and transwell migration and invasive-ness assays. Lastly, Western blot was performed to explore the potential mechanism. RESULTS: In this investigation, qRT-PCR results indicated that JMJD3 expression in above-mentioned tumor tissues was conspicuously higher than that in normal tissues. In addition, compared with patients with low level of JMJD3, patients with high level of JMJD3 had a higher incidence of lymphatic metastasis and distant metastasis and a lower overall survival rate. Meanwhile, the proliferation, invasiveness and migratory capacity of cells in the sh-JMJD3 group was conspicuously decreased when compared with the cells in negative control group. Western Blot results indicated that the levels of key proteins in EMT signaling pathway such as E-cadherin, N-cadherin, Vimentin, TGF-beta, and MMP-9 were notably decreased in sh-JMJD3 group. Besides, the addition of TGF-beta cytokines synergistically promoted the malignant progression of NSCLC induced by JMJD3. CONCLUSIONS: JMJD3 expression was found conspicuously increased in NSCLC, which might be close relevant to NSCLC lymphatic or distant metastasis as well as patients' poor prognosis. Therefore, we speculated that JMJD3 could promote invasiveness and migratory capacity of non-small cell lung cancer cells by activating EMT process.