ANRIL inhibits p15(INK4b) through the TGFβ1 signaling pathway in human esophageal squamous cell carcinoma

Deyu Chen; Zhaoyue Zhang; Chaoming Mao; Yuepeng Zhou; Lichao Yu; Yue Yin; Shi Wu; Xiao Mou; Yan Zhu

doi:10.1016/j.cellimm.2014.03.015

ANRIL inhibits p15(INK4b) through the TGFβ1 signaling pathway in human esophageal squamous cell carcinoma

Cell Immunol. 2014 May-Jun;289(1-2):91-6. doi: 10.1016/j.cellimm.2014.03.015. Epub 2014 Apr 3.

Authors

Deyu Chen¹, Zhaoyue Zhang², Chaoming Mao³, Yuepeng Zhou², Lichao Yu⁴, Yue Yin¹, Shi Wu¹, Xiao Mou¹, Yan Zhu²

Affiliations

¹ Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
² School of Clinical Medicine, Jiangsu University, Zhenjiang 212013, China.
³ Institute of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China. Electronic address: jq1001@ujs.edu.cn.
⁴ Department of Thoracic Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.

PMID: 24747824
DOI: 10.1016/j.cellimm.2014.03.015

Abstract

The INK4b-ARF-INK4a gene cluster encodes three tumor suppressors: p15(INK4b), p14(ARF), and p16(INK4a). Antisense non-coding RNA in the INK4 locus (ANRIL) is transcribed in the opposite direction from this gene cluster. Recent studies suggest that ANRIL represses the expression of p15(INK4b), p14(ARF), and p16(INK4a); however, the underlying mechanism is unclear. In this study, the expressions of ANRIL in human esophageal squamous cell carcinoma (ESCC) tissues and matched adjacent non-tumor tissues were examined by quantitative real-time polymerase chain reaction. Compared with matched adjacent non-tumor tissues, the expression levels of ANRIL in ESCC tissues were significantly increased. Furthermore, inhibition of ANRIL was found to increase the expression of p15(INK4b) and transforming growth factor β1 (TGFβ1) and depletion of ANRIL in ESCC cell lines may inhibit cellular proliferation. Thus, our findings suggest a significant role of ANRIL in the occurrence and development of ESCC through TGFβ1 signaling pathways.

Keywords: Antisense non-coding RNA in the INK4 locus; Esophageal squamous cell carcinoma; Long non-coding RNA; Transforming growth factor β1; p15(INK4b).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / metabolism
Cell Cycle / genetics
Cell Line, Tumor
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p15 / antagonists & inhibitors
Cyclin-Dependent Kinase Inhibitor p15 / biosynthesis
Cyclin-Dependent Kinase Inhibitor p15 / genetics*
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / metabolism
Esophageal Squamous Cell Carcinoma
Humans
RNA, Long Noncoding / antagonists & inhibitors
RNA, Long Noncoding / biosynthesis
RNA, Long Noncoding / genetics*
Signal Transduction / genetics
Smad Proteins / metabolism
Transforming Growth Factor beta1 / biosynthesis
Transforming Growth Factor beta1 / genetics*
Tumor Suppressor Proteins / genetics

Substances

CDKN2B antisense RNA, human
Cyclin-Dependent Kinase Inhibitor p15
RNA, Long Noncoding
Smad Proteins
Transforming Growth Factor beta1
Tumor Suppressor Proteins