Let-7c inhibits metastatic ability of mouse hepatocarcinoma cells via targeting mannoside acetylglucosaminyltransferase 4 isoenzyme A

Int J Biochem Cell Biol. 2014 Aug;53:1-8. doi: 10.1016/j.biocel.2014.04.012. Epub 2014 Apr 24.

Abstract

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.

Keywords: Glycosyl-transferase; Let-7c; Mgat4a; MicroRNA; N-glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Glycosylation
  • Humans
  • Isoenzymes / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Lymphatic Metastasis / genetics
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • N-Acetylglucosaminyltransferases / biosynthesis*
  • N-Acetylglucosaminyltransferases / genetics
  • Neoplasm Invasiveness / genetics*
  • RNA, Small Interfering / genetics

Substances

  • Isoenzymes
  • MicroRNAs
  • RNA, Small Interfering
  • N-Acetylglucosaminyltransferases