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.
Highlights
It is well accepted that colorectal cancer (CRC) is the third most common type of cancer and a major cause of cancer-related mortality worldwide [1, 2]
17 members of the Poly (ADP-ribose) polymerases (PARPs) family have been identified, and the PARP family is involved in the development of various diseases including cancer [9, 10].PARP6 is a new member of the PARP family, and the roles and underlying mechanisms of PARP6 in CRC remain unknown
Reduced expression of PARP6 protein was observed in CRC tissues, in comparison with normal adjacent colon tissues by immunohistochemical analysis and Western blot analysis
Summary
It is well accepted that colorectal cancer (CRC) is the third most common type of cancer and a major cause of cancer-related mortality worldwide [1, 2]. The presence of Poly (ADP-ribosyl) ation activity was originally suggested in the 1960s [3, 4]. PARPs are multifunctional nuclear proteases that mediate posttranslational protein modification in the process of polyADP-glycosylation [5, 6]. Post-translational modification of proteins by poly (ADP-ribosyl) ation is involved in a variety of biological process including DNA repair, chromatin structural regulation, gene transcription, cell cycle progression and cell death [5, 6]. The PARP family is correlated with the development of various diseases [9, 10]. Among the PARPs, PARP-1, which produces polymers of ADP-ribose (PAR) using NAD+
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