Differential expression of APE1 in hepatocellular carcinoma and the effects on proliferation and apoptosis of cancer cells

Abstract

2. Materials and Methods 2.1. Tissue samples and main reagents Tissue samples and experimental cells: HCC tissue microarrays were purchased from Shanghai Outdo Biotech (model HLivH160CS01); there were 80 cases of HCC, 1 each at cancer/paracancerous site. TNM staging was available, clinical phase 1, 2, 3 and 4, Summary This research aimed to investigate the differential expression of apurinic-apyrimidinic endonuclease 1 (APE1) in hepatocellular carcinoma (HCC) tissues and cells and the effects on proliferation and apoptosis of cancer cells. Immunohistochemical techniques were used to detect the expression of APE1 in 80 cases of HCC and the corresponding paracancerous tissue microarrays; meanwhile, Western blots were used to detect the expression of APE1 in both human HCC BEL-7402, BEL-7405, HCC-9204, Hep3B, HepG2, SMMC-7721 and Huh-7 cells, and normal hepatocyte L-02 cells. The relationship between APE1 expression and clinical pathological characteristics of HCC was statistically analyzed. APE1 shRNA vector was constructed in Hep 3B cells to establish a stably transfected cell line, using Western blots to determine the interference efficiency. Cell proliferation activity was detected with MTT assays, while apoptosis was detected with the Annexin V-FITC/PI double-labeling technique. The expression of APE1 in HCC tissues and cells was significantly up-regulated, and its expression was significantly different from TNM staging and histopathological grading. Down-regulation of APE1 expression significantly reduced the proliferative activity and increased the apoptosis rate of Hep 3B cells. In conclusion, APE1 demonstrates cancer progression potential at the clinical, tissue and cell level. It provides a new idea and theoretical basis for APE1-based clinical diagnosis, prognosis determination and molecular targeted therapy in treatment of HCC.

Architecture of The Human Ape1 Interactome Defines Novel Cancers Signatures

“…These 11 gene sets were then subjected to survival analysis for a better understanding of their role according to a clinical perspective. LIHC, LUAD and PAAD networks, which were composed of bad prognostic genes in high percentages, confirmed previous studies on the important role of APE1 in these cancers [52][53][54][55][57][58][59][60][61][62][63][64][65] . Kaplan-Meier estimation was used to calculate survival probability associated with these genes; the ones having significantly lower survival prognosis (p < 0.05) were used to create cancer-specific PPI subnetworks ( Fig.…”

“…In order to focus our attention on the most relevant cancer types, we based our bioinformatic analysis on the eleven datasets having the highest number of bad prognostic genes. Among those, we were interested in particular in liver (LIHC) [52][53][54][55][56] , lung (LUAD) [57][58][59][60] and pancreatic (PAAD) [61][62][63][64][65] cancer datasets, as the essential role of APE1 in the tumorigenic processes of these cancer types is already well established. Notably, the LUAD dataset was the third having the highest number of bad prognostic genes (n = 153).…”

“…Because of the strong interest in APE1 as a prognostic factor in liver [52][53][54][55][56] and pancreatic cancers [61][62][63] , we applied the same representation also to the LIHC (Fig. 6D-F) and PAAD datasets ( Fig.…”

Design, synthesis and biological evaluation of 4-piperidin-4-yl-triazole derivatives as novel histone deacetylase inhibitors

“…Then the cells were incubated with indicated concentrations of the compounds for 72 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) was subsequently added for an extra 3 h of incubation. The MTT formazan precipitate was dissolved in DMSO, and the absorbance was measured at a wavelength of 570 nm by a Spectramax M5 microtiter plate luminometer (Molecular Devices, Sunnyvale, CA, USA) (24)(25)(26). Experiments were performed in triplicate and repeated for three times.…”

Knockdown expression of <i>MECR</i>, a novel gene of mitochondrial FAS II inhibits growth and colony-formation, promotes apoptosis of hepatocelluar carcinoma cells

“…Poor prognosis means finding more accurate biomarkers to predict a patient's prognosis and finding a more effective therapeutic gene targets are top priority for current research (5,6). Although some carcinogenic mechanisms and molecular mechanisms of HCC have been studied and proved, including genomic instability (7,8), gene mutation (9,10), carcinogenic and tumor suppressor gene expression (11), signaling pathways and so on (12)(13)(14)(15), the overall and exact molecular pathology of HCC remains unclear. Still need a lot of basic scientific research and studies.…”