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

// Guangying Qi 1, 2, * , Yasusei Kudo 3, * , Bo Tang 4, * , Tian Liu 1 , Shengjian Jin 1 , Jing Liu 1 , Xiaoxu Zuo 1 , Sisi Mi 1 , Wenhuan Shao 1 , Xiaojuan Ma 1 , Takaaki Tsunematsu 3 , Naozumi Ishimaru 3 , Sien Zeng 1 , Masaaki Tatsuka 5 , Fumio Shimamoto 2 1 Department of Pathology and Physiopathology, Guilin Medical University, Guilin 541004, People’s Republic of China 2 Department of Health Sciences, Prefectural University of Hiroshima, Hiroshima 734-8558, Japan 3 Department of Oral Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan 4 Department of Hepatobiliary Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541000, People’s Republic of China 5 Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Hiroshima 727-0023, Japan * These authors have contributed equally to this work Correspondence to: Sien Zeng, e-mail: zse@glmc.edu.cn Masaaki Tatsuka, e-mail: tatsuka@pu-hiroshima.ac.jp Fumio Shimamoto, e-mail: simamoto@pu-hiroshima.ac.jp Keywords: PARP6, Survivin, colorectal cancer, tumor suppressor, prognosis Received: January 15, 2016      Accepted: February 15, 2016      Published: February 25, 2016 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.