Long non-coding RNA HAND2-AS1 inhibits invasion and metastasis in endometrioid endometrial carcinoma through inactivating neuromedin U

Yang, Xueying; Wang, Chi Chiu; Lee, Wayne Yuk Wai; Trovik, Jone; Chung, Tony Kwok Hung; Kwong, Joseph

Abstract

Endometrioid endometrial carcinoma (EEC) is one of the common causes of cancer-related mortality in women. Mounting evidences suggest that long noncoding RNAs (lncRNAs) function in multiple cancers. In this study, we discovered that HAND2-AS1, a lncRNA transcribed antisense adjacent to Heart and Neural Crest Derivatives Expressed 2 (HAND2) in chromosome 4q33-34, is significantly down-regulated in EEC. HAND2-AS1 and HAND2 were frequently down-regulated in EEC tissues, especially in poor differentiated tumor tissues. Down-regulation of HAND2-AS1 and HAND2 was correlated with tumor grade, lymph node metastasis and recurrence of EEC patients. HAND2-AS1 and HAND2 were co-downregulated by promoter DNA hypermethylation in EEC. Overexpression of HAND2-AS1 in EEC cells demonstrated that HAND2-AS1 suppressed migration and invasion of EEC cells. Similarly, overexpression of HAND2 also inhibited migration and invasion EEC cells indicating that HAND2-AS1 and HAND2 had a concordant role in the progression of EEC. However, HAND2 was not regulated by HAND2-AS1 in EEC. Furthermore, the anti-tumorigenic effect of HAND2-AS1 was mediated by down-regulating NMU, which has an oncogenic role in EEC. Our findings therefore provide the first evidence that HAND2-AS1 is a critical tumor suppressor in EEC.

Citation

Yang, X., Wang, C. C., Lee, W. Y. W., Trovik, J., Chung, T. K. H., & Kwong, J. (2018). Long non-coding RNA HAND2-AS1 inhibits invasion and metastasis in endometrioid endometrial carcinoma through inactivating neuromedin U. Cancer Letters, 413, 23-34. https://doi.org/10.1016/j.canlet.2017.10.028

• Journal Article Type: Article
• Acceptance Date: Oct 19, 2017
• Online Publication Date: Oct 26, 2017
• Publication Date: Jan 28, 2018
• Deposit Date: Jun 23, 2023
• Journal: Cancer Letters
• Print ISSN: 0304-3835
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 413
• Pages: 23-34
• DOI: https://doi.org/10.1016/j.canlet.2017.10.028
• Keywords: Cancer Research; Oncology; LncRNA; HAND2-AS1; HAND2; NMU; Promoter hypermethylation; Endometrial carcinoma
• Additional Information: This article is maintained by: Elsevier; Article Title: Long non-coding RNA HAND2-AS1 inhibits invasion and metastasis in endometrioid endometrial carcinoma through inactivating neuromedin U; Journal Title: Cancer Letters; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.canlet.2017.10.028; Content Type: article; Copyright: © 2017 Elsevier B.V. All rights reserved.