SUZ12 Is Involved In Progression Of Non-small-cell Lung Cancer By Promoting Cell Proliferation And Metastasis

Background:Non-small-cell lung cancer (NSCLC) is one of the highest mortality malignancies.The main treatment for stage I, Ⅱ and part of Ⅲa (T3N1-2M0; T1-2N2M0; T4N0-1M0 which can completely resected) is surgical excision.It can get good curative effect for Ⅲa from postoperative adjuvant chemotherapy and neoadjuvant chemotherapy.It sounds easy to relapse after radiotherapy and chemotherapy for advanced NSCLC.With the rapid progress of genome era,the important treatment for the mutant NSCLC currently is targeted therapy,supplemented with chemotherapy,radiotherapy and immunotherapy.However,a number of multicenter randomized controlled Phase III clinical experimental studies have discovered that NSCLC targeted drugs prone to the emergence of drug-resistant mutations,it is still dissatisfied for clinical efficacy.So to find new drug targets for NSCLC becomes an urgent problem to be solved.The suppressor of zeste-12 protein (SUZ12),a core subunit of polycomb repressive complex 2 (PRC2), is implicated in transcriptional silencing by generating di-and tri-methylation of lysine 27 on histone H3 (H3K27Me3). Although SUZ12 is up-regulated and known to be of great importance in several human cancer tumorigenesis,limited data are available on functional role of SUZ12 in non-small-cell lung cancer.Objective:To investigate the expression level of SUZ12 in NSCLC specimens and NSCLC cells.Figure out the correlation between the expression level of SUZ12 and their clinical significance.To prove the infulence of SUZ12 towards to the biological effects of NSCLC in vitro.Try to elucidate the molecular biological mechanisms of SUZ12.Materials and Methods:In clinical NSCLC specimens, we used qRT-PCR to dectect the expression of SUZ12 in 40 tumor tissues and Western blot in 4 tumor tissues,contrast to adjacent normal tissues.SUZ12-siRNA was transiently transfected into NSCLC cells line (A549 and SPC-A1) after designed and utilized to inhibit the expression of SUZ12 gene, then observated the status of cells proliferation, migration and invasion in A549 and SPC-A1 with MTT assays, colony formation assays and Transwell assays.Western blot dectect the expression of transcription factor E2F1,potential metastasis promoters Rho associated, coiled-coil-containing protein kinase 1(ROCK1) and roundabout homolog 1 (ROBO1) after SUZ12 knockdown. Statistic analysis was conducted using SPSS 18.0 software. Two-tailed Student’s t test and Chi-square analysis were performed to analyze the data. The results were expressed as the mean±S.D. P value less than 0.05 was considered to be statistically significant.Results:The expression levels of SUZ12 is up-regulated in NSCLC tissues by qRT-PCR and Western blot; The expression levels of SUZ12 is up-regulated in cell lines by Western blot.The proliferation、migration and invasion of NSCLC cells are significantly suppressed after the down-regulating of SUZ12.Western blot results revealed that SUZ 12 knockdown significantly reduced the expression level of E2F1、 ROCK1 and ROBO1 protein.Conclusions:SUZ12 may involve in NSCLC oncogenesis,development and metastasis by regulating NSCLC cells proliferation and metastasis partly via reducing E2F1, ROCK1, and ROBO1.It may represent a new potential diagnostic marker for NSCLC and may be a novel therapeutic target for NSCLC intervention.