The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma

// Ying Wu 1, * , Hongbing Liu 1, * , Xuefei Shi 1 , Yanwen Yao 1 , Wen Yang 1 , Yong Song 1 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China * These authors have contributed equally to this work Correspondence to: Yong Song, e-mail: yong.song6310@gmail.com Keywords: lncRNAs, HNF1A-AS1, proliferation, metastasis, lung adenocarcinoma Received: October 31, 2014 Accepted: January 28, 2015 Published: March 26, 2015 ABSTRACT Long noncoding RNAs (lncRNAs) have emerged as key regulators of tumor development and progression. The lncRNA HNF1A-antisense 1 (HNF1A-AS1) is a 2455-bp transcript on chromosome 12 with a potential oncogenic role in esophageal adenocarcinoma. Nevertheless, current understanding of the involvement of HNF1A-AS1 in lung adenocarcinoma tumorigenesis remains limited. In this study, we analyzed the roles of HNF1A-AS1 in 40 lung adenocarcinoma tissues and five lung cancer cell lines. Our results showed that HNF1A-AS1 was significantly up-regulated in lung adenocarcinoma tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with TNM stage, tumor size, and lymph node metastasis. The UCSC Cancer Genomics Browser’s Kaplan-Meier plot suggested that patients in the high HNF1A-AS1 expression subgroup experienced worse overall survival compared to the low expression subgroup. Moreover, HNF1A-AS1 was determined to promote tumor proliferation and metastasis, both in vitro and in vivo , by regulating cyclin D1, E-cadherin, N-cadherin and β-catenin expression. In addition, the binding of HNF1A-AS1 to DNMT1 may explain its regulation of E-cadherin. In conclusions, we demonstrated that increased HNF1A-AS1 expression could regulate cell proliferation and metastasis and identified it as a poor prognostic biomarker in lung adenocarcinoma.