title: Glycogenes mediate the invasive properties and chemosensitivity of human hepatocarcinoma cells.
abstract: Aberrant cell-surface glycosylation patterns are present on tumors and have been linked to tumor progression. This study aimed to identify the alterations of glycogene and N-glycan involved in tumor invasion, tumorigenicity and drug resistance in MHCC97-H and MHCC97-L human hepatocarcinoma cell lines, which have high, low metastatic potential, respectively. Using real-time PCR for quantification of glycogene and FITC-lectin binding for glycan profiling, we found that the expression of glycogenes and glycan profiling were different in MHCC97-H cells, as compared to those in MHCC97-L cells. We silenced the expression levels of glycogenes MGAT3 and MGAT5, which were over-expressed in MHCC97-L and MHCC97-H cells. Knockdown of MGAT3 expression promoted MHCC97-L cells invasion and increased resistance to 5-fluorouracil in vitro. The silencing of MGAT5 in MHCC97-H cells inhibited invasion and increased sensitivity to 5-fluorouracil in vitro. Further analysis of the N-glycan regulation by tunicamycin application or PNGase F treatment in MHCC97-H and MHCC97-L cells showed partial inhibition of N-glycan glycosylation, decreased invasion, tumorigenicity and increased sensitivity to 5-fluorouracil both in vitro and in vivo. These findings suggest that alterations of glycogene and N-glycan in human hepatocarcinoma cells correlate with tumor invasion, tumorigenicity and sensitivity to chemotherapeutic drug, and have significant implications for the development of treatment strategies.
authors.affiliation: College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
authors.forename: Chunqing
authors.initials: C
authors.lastname: Liu
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D059467:Transcriptome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D037102:Lectins; D016695:Glycosyltransferases; D005472:Fluorouracil