SiRNA‐targeted carboxypeptidase D inhibits hepatocellular carcinoma growth

Abstract

Carboxypeptidase D (CPD), a membrane-bound metallocarboxypeptidase that functions as a docking receptor for duck hepatitis B virus, is frequently overexpressed in human cancers. We have explored its expression pattern, clinical significance, and biological function of CPD in hepatocellular carcinoma (HCC). CPD expression was markedly elevated in HCCs relative to adjacent non-tumor liver tissues, as determined by quantitative real-time polymerase chain reaction and Western blot analysis. Immunohistochemistry showed that 164 of 400 (41%) HCCs had high expression of CPD. CPD overexpression was significantly associated with serum levels of hepatitis B surface antigen and hepatitis B e antigen, liver cirrhosis, pathological grade, and intrahepatic metastasis. Knockdown of endogenous CPD expression in Huh7 HCC cells by RNA interference reduced cell proliferation, blocked the cell cycle at G1 phase, and increased apoptosis. Many genes implicated in cell-cycle regulation, including P21waf1, P27 Kip1, SKP2, and CDC2, were deregulated by CPD downregulation. Thus CPD is frequently upregulated in HCC, and targeting CPD inhibits HCC cell proliferation through induction of G1 cell-cycle arrest and apoptosis, thereby providing a potential therapeutic target for this malignancy.

Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma

“…The correlation between some of the proteins selected for the verification analysis and HCC has been separately and independently reported previously (Table ). ,− Thus, the comprehensive expression profiles presented in this analysis provide supporting evidence for the involvement of the verified proteins in HCC development. To our knowledge, this is the first report showing the overexpression of DDX39, FBLN5, MARCKS, and SERPINH1 in association with HCC.…”

“… a The analysis was done on 31 HCC and 31 adjacent nontumorous samples. Bold formatted proteins are with ≤0.05 FDR p -value. b Proteins which were reported in previous studies in association with HCC. ,− c Paired t test. d FDR adjusted p -value according to Benjamini and Hochberg. …”

Novel and Rare Fusion Transcripts Involving Transcription Factors and Tumor Suppressor Genes in Acute Myeloid Leukemia

“…Data from the TCGA Fusion Gene Database showed that the some of the candidate genes form chimeras with a variety of partners in different tumor types, suggesting that they might locate in genomic regions prone to chromosomal rearrangements [46,47] and/or have a role in carcinogenesis. The most frequently altered genes were CPD and CNOT2, whose overexpression was associated with survival, inhibition of apoptosis and angiogenesis in different cancer types [22,[48][49][50][51]. Regarding the other genes that were rarely rearranged across cancer, they might participate to the leukemic phenotype, even though not being the driver of transformation.…”

Prolactin‐ and testosterone‐induced carboxypeptidase‐D correlates with increased nitrotyrosines and Ki67 in prostate cancer

“…Likewise, CPD immunostaining is higher in PCa than in benign prostate tissues . CPD levels are also elevated in hepatocellular carcinoma, as compared to benign liver tissue, whereas knockdown of endogenous CPD expression in Huh7 liver carcinoma cells reduces cell proliferation and increases apoptosis .…”