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; Qiang Sun; Lufei Zhang; Xiaohu Zhou; Xiaofei Cheng; Dongkai Zhou; Feng Ye; Jianjiang Lin; Weilin Wang

doi:10.18632/oncotarget.19956

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

Oncotarget. 2017 Aug 3;8(41):70642-70652. doi: 10.18632/oncotarget.19956. eCollection 2017 Sep 19.

Authors

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 Ye¹, Jianjiang Lin¹, Weilin Wang^{2

3

4}

Affiliations

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.

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.

Keywords: HOXA11 antisense RNA (HOXA11-AS); colorectal cancer (CRC); liver metastasis; long noncoding RNA (lncRNA); peptidyl arginine deiminase 2 (PADI2).