LncRNA HOTAIRM1/HOXA1 Axis Promotes Cell Proliferation, Migration And Invasion In Endometrial Cancer
LncRNA HOTAIRM1/HOXA1 Axis Promotes Cell Proliferation, Migration And Invasion In Endometrial Cancer
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LncRNA HOTAIRM1/HOXA1 轴促进子宫内膜癌细胞增殖、迁移和侵袭
DOI：
10.2147/ott.s222334
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Wang, Danbo
中科院分区：
文献类型：
--
作者：
Li, Xianli;Pang, Li;Wang, Danbo
背景：长链非编码RNA（lncRNA）微阵列筛选先前确定HOXA转录反义RNA骨髓特异性1（HOTAIRM 1）在I型子宫内膜癌（EC）中显著上调。本研究旨在确定HOTAIRM 1及其正义转录本HOXA 1在I型EC发生和发展中的潜在作用。方法采用实时定量聚合酶链反应（qRT-PCR）和蛋白质印迹法检测I型EC组织中HOTAIRM 1和HOXA 1的表达水平，并结合临床资料进行分析。功能获得或丧失实验用于研究HOTAIRM 1和HOXA 1在I型EC中的生物学功能，包括体外和体内。结果HOTAIRM 1和HOXA 1在I型EC组织中的表达明显上调。HOTAIRM 1和HOXA 1的表达与国际妇产科联盟（FIGO）的临床分期和淋巴结转移密切相关。HOTAIRM 1与HOXA 1的表达呈显著相关。HOTAIRM 1的敲低可显著抑制细胞的增殖、迁移、侵袭和上皮-间质转化（EMT），而HOTAIRM 1的过表达则导致相反的效应。此外，我们确定HOTAIRM 1作为HOXA 1基因在I型EC细胞中表达的调节因子。作为一种癌基因，HOXA 1的沉默还通过抑制细胞增殖、迁移和侵袭而对肿瘤产生抑制作用。此外，我们还证实了HOTAIRM 1和HOXA 1在体内促进肿瘤生长的作用。结论首次证实HOTAIRM 1是一种癌基因，通过调控HOXA 1促进I型EC细胞增殖、迁移和侵袭。因此，HOTAIRM 1/HOXA 1轴是I型EC的新的潜在预后生物标志物和新的潜在治疗靶点。
Background Long non-coding RNA (lncRNA) microarray screening previously identified that HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) was significantly upregulated in type I endometrial cancer (EC). The present study aimed to determine the potential role of HOTAIRM1 and its sense transcript HOXA1 in the development and progression of type I EC. Methods We detected the expression levels of HOTAIRM1 and HOXA1 in type I EC tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting and analyzed associated clinical data. Gain- or loss-of-function experiments were used to investigate the biological function of HOTAIRM1 and HOXA1 in type I EC, both in vitro and in vivo. Results The expression levels of HOTAIRM1 and HOXA1 were significantly upregulated in type I EC tissues. Furthermore, the expression of HOTAIRM1 and HOXA1 were both significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. The expression of HOTAIRM1 was significantly correlated with that of HOXA1. Knockdown of HOTAIRM1 significantly inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) in vitro, while the over-expression of HOTAIRM1 led to the opposite effects. Moreover, we identified that HOTAIRM1 acts as a regulator for the expression of the HOXA1 gene in type I EC cells. As an oncogene, HOXA1 silencing also caused suppressive effects on tumors by inhibiting cell proliferation, migration and invasion. In addition, we also confirmed the role of HOTAIRM1 and HOXA1 in promoting tumor growth in vivo. Conclusion Our findings are the first to identify that HOTAIRM1 functions as an oncogene to promote cell proliferation, migration and invasion by regulating HOXA1 in type I EC. Therefore, the HOTAIRM1/HOXA1 axis is a novel potential prognostic biomarker and new potential therapeutic target for type I EC.