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  • Title: Long non-coding RNA HAND2-AS1 inhibits invasion and metastasis in endometrioid endometrial carcinoma through inactivating neuromedin U.
    Author: Yang X, Wang CC, Lee WYW, Trovik J, Chung TKH, Kwong J.
    Journal: Cancer Lett; 2018 Jan 28; 413():23-34. PubMed ID: 29107108.
    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.
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