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.

Dongkai Zhou,Dong Chen,Xiaohu Zhou,Weilin Wang,Qiang Sun,Jianjiang Lin,Lufei Zhang,Feng Ye,Xiaofei Cheng

doi:10.18632/oncotarget.19956

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.

Highlights

According to the latest statistics, colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States [1] and the fifth most diagnosed cancer in China [2, 3]
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
To determine the function of HOXA11-AS in CRC metastasis, the transfection of an siRNA targeting HOXA11AS and the overexpression of HOXA11-AS in SW480 cells www.impactjournals.com/oncotarget were validated by Quantitative real-time polymerase chain reaction (qRT-PCR) analysis

Summary

Introduction

According to the latest statistics, colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States [1] and the fifth most diagnosed cancer in China [2, 3]. Metastasis is the primary cause of death for CRC patients, and the liver is the primary site of metastatic lesions due to portal drainage [4]. The early diagnosis and treatment of liver metastasis in CRC patients are important for improved mortality and survival. The diagnosis of liver metastasis is based on imaging; existing methods for the early diagnosis of liver metastasis are far from sufficient [5]. Long non-coding RNAs (lncRNAs; 200–100,000 nucleotides in length) participate in the biological and pathological processes of CRC, including apoptosis, proliferation, and metastasis [4, 6, 7]. Emerging evidence indicates that lncRNAs act as competing endogenous RNAs (ceRNAs) or molecular sponges that modulate microRNAs (miRNAs) [8]. Most functions of lncRNAs have not been clarified

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Conclusion