title: Silencing of ST6GalNAc I suppresses the proliferation, migration and invasion of hepatocarcinoma cells through PI3K/AKT/NF-κB pathway.
abstract: ST6GalNAc I is the major Sialyl-Tn antigen (STn) synthase that is highly correlated with tumor invasion and metastasis. However, the roles and molecular mechanisms by which ST6GalNAc I mediates the malignant phenotypes of hepatocarcinoma cells still remain poorly unknown. In this study, we investigated the expression of STn and ST6GalNAc I in mouse hepatocarcinoma cell lines Hca-F, Hca-P, and Hepa1-6, which have different metastatic potential, as compared with normal mouse liver cell line IAR-20. The results showed that the expression of ST6GalNAc I and STn in Hca-F and Hca-P cells was much higher than that in Hepa1-6 and IAR20 cells. Knockdown of ST6GalNAc I by shRNA in Hca-F cells significantly decreased the expression of STn and inhibited the growth of tumor cells in vitro and in vivo. This reduction of ST6GalNAc I expression also led to the decreased migration and invasion of Hca-F cells. Furthermore, we found that ST6GalNAc I knockdown inhibited the expression levels of PI3k, p-Akt473, p-Akt308, NF-κB, and their downstream molecules. Together, our results suggest a role of ST6GalNAc I in promoting the growth and invasion of hepatocarcinoma cells through regulating PI3K/AKT signaling, and ST6GalNAc I might be a promising marker for the prognosis and therapy of hepatocarcinoma.
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Lvshun South Road, Dalian, 116044, Liaoning Province, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Lvshun South Road, Dalian, 116044, Liaoning Province, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Lvshun South Road, Dalian, 116044, Liaoning Province, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Surgery, The Third People's Hospital of Dalian, Affiliated Hospital of Dalian Medical University, Dalian, 116000, Liaoning Province, China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian, 116044, Liaoning Province, China.
authors.lastname: Pawan
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Lvshun South Road, Dalian, 116044, Liaoning Province, China. wangshujing@dlmedu.edu.cn.
authors.forename: Shujing
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D016328:NF-kappa B; C055491:sialosyl-Tn antigen; D012799:Sialyltransferases; C038525:CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Hepatocarcinoma; Invasion; Migration; Proliferation; ST6GalNAc I; STn