Molecula Mechanism Of Knockdown Of HS6ST2 To Activate Caspase-3/PARP1 Signaling Pathway To Promote Apoptosis In Non-small Cell Lung Cancer Cells

Background:Heparan Sulfate 6-O-Sulfotransferase 2(HS6ST2),a member of the heparan sulfate(HS)sulfotransferase family,which catalyzes transfer of a sulfo group from 3'-phosphoadenosime 5'-phosphosulfate(PAPS)to the 6-OH of the N-sulfoglucosamine(GlcN).Abnormal expression of HS6ST2 has been known to the progression of multiple human cancers,including ovarian cancer,gastric cancer,colorectal cancer and pancreatic cancer.Nevertheless,the biological function of HS6ST2 in the progression and development of non-small cell lung cancer(NSCLC)remains unclear.-Methods:In this study,HS6ST2 was identified as an up-regulated gene in NSCLC by RNA microarray analysis and gene expression data from The Cancer Genome Atlas(TCGA)database.To measure the function of HS6ST2 in NSCLC cells and its underlying mechanisms,we use the Small interfering RNA(siRNA)to silence HS6ST2 mRNA and protein expression.Subsequently CCK-8 assay,plate cloning assay and Real-time Cell Analyzer(RTCA)were used to detected cell proliferation,flow cytometry to analyze cell cycle and cell apoptosis,Transwell chamber and RTCA to detect cell migration and invasion,and Western blotting was used to detect protein expression.Results:Cell proliferation,migration and invasion ability were inhibited in NCI-H292 and GLC after transfected siHS6ST2 and the transition G1 phase to S phase was also hindered.The protein expression level of Cyclin D1,Bcl-2,E-cadherin and vimentin were down-regulated,at the same time active-Caspase-3 and cleaved-PARP1 were up-regulated.Conclusion:Our results suggest that upregulation of HS6ST could inhibit NSCLC cell apoptosis via the Caspase-3/PARP1 signaling pathway.Therefore,we can speculate that HS6ST2 may be a potential prognostic and therapeutic target for NSCLC.