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

被引:158
作者
Wu, Ying [1 ]
Liu, Hongbing [1 ]
Shi, Xuefei [1 ]
Yao, Yanwen [1 ]
Yang, Wen [1 ]
Song, Yong [1 ]
机构
[1] Nanjing Univ, Sch Med, Jinling Hosp, Dept Resp Med, Nanjing 210008, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
lncRNAs; HNF1A-AS1; proliferation; metastasis; lung adenocarcinoma; EPITHELIAL-MESENCHYMAL TRANSITION; E-CADHERIN; POOR-PROGNOSIS; CANCER; METHYLATION; DNMT1; TRANSCRIPTION; EXPRESSION; CYCLIN-D1; EVOLUTION;
D O I
10.18632/oncotarget.3247
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 beta-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.
引用
收藏
页码:9160 / 9172
页数:13
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