PARP6 acts as a tumor suppressor via downregulating Survivin expression in colorectal cancer

Abstract

Poly (ADP-ribose) polymerases (PARPs) are enzymes that transfer ADP-ribose groups to target proteins and are involved in a variety of biological processes. PARP6 is a novel member, and our previous findings suggest that PARP6 may act as a tumor suppressor via suppressing cell cycle progression. However, it is still unclear that PARP6 function besides growth suppression in colorectal cancer (CRC). In this study, we examined tumor suppressive roles of PAPR6 in CRC cells both in vitro and in vivo. We found that PARP6 inhibited colony formation, invasion and migration as well as cell proliferation. Moreover, ectopic overexpression of PARP6 decreased Survivin expression, which acts as an oncogene and is involved in apoptosis and mitosis. We confirmed the inverse correlation between PARP6 and Survivin expression in CRC cases by immunohistochemistry. Importantly, CRC cases with downregulation of PARP6 and upregulation of Survivin showed poor prognosis. In summary, PARP6 acts as a tumor suppressor via downregulating Survivin expression in CRC. PARP6 can be a novel diagnostic and therapeutic target together with Survivin for CRC.

Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

“…Notable genes include: ZFP82 , which is epigenetically silenced and suspected to function as a tumor suppressor (Xiao et al, 2014) (Yu et al, 2015) (Fan et al, 2016); PARP6 hypermethylation (Honda et al, 2016) (Qi et al, 2016); DNAJC15, which is hypermethylated in a number of tumor types (Ehrlich et al, 2002; Lindsey et al, 2006), and whose inactivation has been associated with chemotherapeutic drug resistance in breast (Fernandez-Cabezudo et al, 2016) and ovarian cancers (Rein et al, 2011). We also identified genes that were epigenetically silenced at low prevalence through manual examination of the genes known to be important in cancer, including BRCA1 and MGMT (each silenced in one case).…”

Knockdown of PARP6 or survivin promotes cell apoptosis and inhibits cell invasion of colorectal adenocarcinoma cells

“…It was demonstrated that overexpression of PARP6 suppressed the cell growth of HeLa cells (14). PARP6 was found to be negatively correlated with the Ki-67 proliferation index, and may be a marker for better prognosis in colorectal adenocarcinoma (13,14). A recent study demonstrated that PAPR6 inhibited colony formation, invasion and cell proliferation in human colorectal adenocarcinoma cell line SW480 (13), and indicated an interaction between the overexpression of PARP6 and the downregulation of survivin.…”

“…They play important roles in physiological and pathophysiological processes. Recently, it was shown that PARP6 likely encodes tumor suppressors, and an increase in its methylation was associated with a poor prognosis of various cancer, including hepatoblastoma, colorectal adenocarcinoma (9), breast (10), pancreatic (11), breast (12) and colorectal cancer (13). Among the PARPs, PARP1 is the member which has been studied most extensively.…”

Epigenetically Silenced Candidate Tumor Suppressor Genes in Prostate Cancer: Identified by Modeling Methylation Stratification and Applied to Progression Prediction

“…The facts include (i) the tumor suppression functions of the 10 genes have been demonstrated or suggested in previous publications ( Table 2; refs. [19][20][21][22][23][24][25][26][27][28][29][30][31] and (ii) the methylation statuses in a tumor are well determined by the clearly stratified across-tumor methylation profiles. We also note that these genes can be divided into three categories, representing an uncompleted but a typical taxonomy of potential epi-TSGs.…”