Rabbit Anti-Human NDRG3 Polyclonal Antibody

microRNAs (miRNAs) are short, non-coding RNAs with post-transcriptional regulatory functions that participate in diverse biological pathways. miR-122, a liver-specific miRNA, has been found to be down-regulated in hepatocellular carcinoma (HCC) and HCC-derived cell lines. In this study, miR-122 was down-regulated in the hepatitis B virus (HBV)-related HCC cell line HepG2.2.15 compared to HepG2. NDRG3, a member of the N-myc downstream-regulated gene (NDRG) family, was up-regulated in HepG2.2.15 and was identified as a target gene-Of miR-122. An inverse correlation between the expression of miR-122 and the NDRG3 protein was noted in HBV-related HCC specimens. The transfection of the miR-122 expression vector into the HepG2.2.15 cell line repressed the transcription and expression of NDRG3, which subsequently reversed the malignant phenotype of the cells. The replication of HBV, expression of viral antigens and proliferation of cells were significantly inhibited by restoration of miR-122. The data demonstrate that miR-122 plays an important role in HBV-related hepatocarcinogenesis by targeting NDRG3. Thus, miR-122 and NDRG3 represent key diagnostic markers and potential therapeutic targets for HBV-related HCC.

The N-Myc downstream-regulated gene (NDRG) family belongs to the alpha/beta-hydrolase fold and is known to exert various physiologic functions in cell proliferation, differentiation, and hypoxia-induced cancer metabolism. In particular, NDRG3 is closely related to proliferation and migration of prostate cancer cells, and recent studies reported its implication in lactate-triggered hypoxia responses or tumorigenesis. However, the underlying mechanism for the functions of NDRG3 remains unclear. Here, we report the crystal structure of human NDRG3 at 2.2 angstrom resolution, with six molecules in an asymmetric unit. While NDRG3 adopts the alpha/beta-hydrolase fold, complete substitution of the canonical catalytic triad residues to non-reactive residues and steric hindrance around the pseudo-active site seem to disable the alpha/beta-hydrolase activity. While NDRG3 shares a high similarity to NDRG2 in terms of amino acid sequence and structure, NDRG3 exhibited remarkable structural differences in a flexible loop corresponding to helix alpha 6 of NDRG2 that is responsible for tumor suppression. Thus, this flexible loop region seems to play a distinct role in oncogenic progression induced by NDRG3. Collectively, our studies could provide structural and biophysical insights into the molecular characteristics of NDRG3.