ERManI is a target of miR-125b and promotes transformation phenotypes in hepatocellular carcinoma (HCC).
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.
Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, United States of America.
Shujuan
S
Pan
Xiaoyun
X
Cheng
Hongan
H
Chen
Patricia D
PD
Castro
Michael M
MM
Ittmann
Anne W
AW
Hutson
Susan K
SK
Zapata
Richard N
RN
Sifers
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D061986:MCF-7 Cells; D008361:Mannosidases / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D010641:Phenotype
C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C568343:MAN1B1 protein, human; D008361:Mannosidases