ERManI is a target of miR-125b and promotes transformation phenotypes in hepatocellular carcinoma (HCC)

PLoS One. 2013 Aug 5;8(8):e72829. doi: 10.1371/journal.pone.0072829. Print 2013.


The MAN1B1 gene product, designated ER alpha-1, 2-mannosidase (ERManI), is an enzyme localized in the Golgi complex of mammalian cells. By functioning as a "gate keeper" to prevent the inappropriate secretion of misfolded glycoproteins, it plays a critical role in maintaining protein homeostasis in the mammalian secretory pathway. In the present study, we identified that a conserved motif within the 3'UTR of ERManI is a target of miR-125b, a microRNA frequently down-regulated in numerous types of cancers, including hepatocellular carcinoma (HCC). As predicted, the expression of ERManI is significantly elevated in HCC, as measured by immunohistochemistry in a liver spectrum tissue microarray. Additional analyses using several hepatoma cell lines demonstrated that the elevated ERManI inversely correlates with a diminished intracellular concentration of miR-125b. Moreover, functional studies indicated that RNAi-mediated knock-down of endogenous ERManI was sufficient to inhibit proliferation, migration, and invasion of hepatoma cells. These phenotypical changes occurred in the absence of alterations in global glycoprotein secretion or ER-stress status. Together, these results revealed a novel post-transcriptional regulatory mechanism for ERManI and implied that this molecule contributes to the regulation of carcinogenesis in HCC independent of its function in glycoprotein quality control.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cells, Cultured
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • MCF-7 Cells
  • Mannosidases / physiology*
  • MicroRNAs / physiology*
  • Phenotype


  • MIRN125 microRNA, human
  • MicroRNAs
  • MAN1B1 protein, human
  • Mannosidases