ANRIL inhibits p15INK4b through the TGFβ1 signaling pathway in human esophageal squamous cell carcinoma

The INK4b-ARF-INK4a gene cluster encodes three tumor suppressors: p15(INK4b), pl4(ARF), and p 6(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 pl 15(INK4b) and transforming growth factor beta 1 (TGF beta 1) 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 TGF beta 1 signaling pathways. (C) 2014 Elsevier Inc. All rights reserved.