Oncotarget

Research Papers:

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 and Weilin Wang _

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Oncotarget. 2017; 8:70642-70652. https://doi.org/10.18632/oncotarget.19956

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Abstract

Dong Chen1,2,3,*, Qiang Sun2,3,4,*, Lufei Zhang2,3,4, Xiaohu Zhou2,3,4, Xiaofei Cheng1,2,3, Dongkai Zhou2,3,4, Feng Ye1, Jianjiang Lin1 and Weilin Wang2,3,4

1Department of Colorectal Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

2Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China

3State Key Laboratory & Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

4Division 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: [email protected]

Jianjiang Lin, email: [email protected]

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.


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