The lncRNA HOXA11-AS functions as a competing endogenous RNA to regulate PADI2 expression by sponging miR-125a-5p in liver metastasis of colorectal cancer

// Dong Chen 1, 2, 3, * , Qiang Sun 2, 3, 4, * , Lufei Zhang 2, 3, 4 , Xiaohu Zhou 2, 3, 4 , Xiaofei Cheng 1, 2, 3 , Dongkai Zhou 2, 3, 4 , Feng Ye 1 , Jianjiang Lin 1 and Weilin Wang 2, 3, 4 1 Department of Colorectal Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 2 Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China 3 State Key Laboratory & Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 4 Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China * These authors have contributed equally to this work Correspondence to: Weilin Wang, email: wam@zju.edu.cn Jianjiang Lin, email: ljjzju@163.com Keywords: colorectal cancer (CRC), HOXA11 antisense RNA (HOXA11-AS), liver metastasis, long noncoding RNA (lncRNA), peptidyl arginine deiminase 2 (PADI2) Received: March 14, 2017 Accepted: June 27, 2017 Published: August 03, 2017 ABSTRACT Several long non-coding RNAs (lncRNAs) play important roles in the regulation of liver metastasis in colorectal cancer (CRC) patients. We previously described the potential involvement of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS), miR-125a-5p, and peptidyl arginine deiminase 2 (PADI2) in promoting liver metastasis in CRC patients. In the present study, we verified the significant upregulation of HOXA11-AS and PADI2, as well as the downregulation of miR-125a-5p, in CRC patients with liver metastasis. Overexpression and knockdown studies of HOXA11-AS or PADI2, as well as gain-/loss-of-function studies of miR-125a-5p, revealed a positive correlation between HOXA11-AS and PADI2 and a negative correlation with miR-125a-5p in the regulation of liver metastasis in CRC cell lines. Overall, we conclude that HOXA11-AS promotes liver metastasis in CRC by functioning as a miR-125a-5p sponge and describe a novel HOXA11-AS–miR-125a-5p–PADI2 regulatory network involved in CRC liver metastasis.