Let-7c inhibits metastatic ability of mouse hepatocarcinoma cells via targeting mannoside acetylglucosaminyltransferase 4 isoenzyme A.
Aberrant glycosylation may promote tumor invasion and metastasis. To investigate whether microRNA (miRNA) is involved in glycosylation-related metastasis, we examined the role of let-7c, a well-known tumor-suppressor miRNA, in glycosylation in murine hepatocarcinoma cell lines Hca-F and Hca-P. We found that let-7c level was higher in Hca-P cells (with lower lymphatic metastasis potential) than in Hca-F cells (with higher lymphatic metastasis potential). Overexpression of let-7c decreased hyper-N-glycosylation of Hca-F cells and repressed their metastatic and invasive ability. Mannoside acetylglucosaminyltransferase 4, isoenzyme A (Mgat4a) is a key glycosyltransferase in the pathway of synthesizing complex N-glycans. Bioinformatics analysis indicates that Mgat4a may be a target of let-7c, which has been verified by dual-luciferase reporter gene assay. Furthermore, the anti-metastatic effect of overexpressed let-7c is similar to that of Mgat4a siRNAs transfection. Hence, our results suggest that let-7c may inhibit the metastatic ability of Hca-F cells, at least partially, via repressing Mgat4a activity.
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
Yanjie
Y
Guo
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
Sheng
S
Li
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
Jianhua
J
Qu
Department of Oncology, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China.
Lin
L
Ye
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
Shujing
S
Wang
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China.
Jianhui
J
Fan
Department of Respiratory Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Qi
Q
Wang
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian 116044, Liaoning, China; School of Life Science and Medicine, Dalian University of Technology, 2 Linggong Road, Dalian 116024, China. Electronic address: jnzhang@dlmedu.edu.cn.
Jianing
J
Zhang
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
D007527:Isoenzymes; D035683:MicroRNAs; D034741:RNA, Small Interfering; D017351:N-Acetylglucosaminyltransferases
Glycosyl-transferase; Let-7c; Mgat4a; MicroRNA; N-glycosylation