LncRNA HOTAIRM1/HOXA1 Axis Promotes Cell Proliferation, Migration And Invasion In Endometrial Cancer.

ONCOTARGETS AND THERAPY(2019)

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Abstract
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.
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Key words
long non-coding RNA,HOTAIRM1,HOXA1,type I endometrial cancer
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