Estrogen promotes the proliferation and migration of endometrial cancer cells by upregulating the expression of lncRNA HOTAIR

Autor: Huixiao Wang, Xulan Ma, Ziwen Jiang, Di Xia, Feng Sui, Fengxian Fu, Yinmei Dai
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Gynecological Endocrinology, Vol 39, Iss 1 (2023)
Druh dokumentu: article
ISSN: 09513590
1473-0766
0951-3590
DOI: 10.1080/09513590.2023.2269248
Popis: Objective Estrogen (E2) is the main contributor to the progression of endometrial cancer (EC). The long noncoding RNA HOX antisense intergenic RNA (HOTAIR) is emerging as a new regulator in several cancer types. This study aimed to investigate the role of HOTAIR in EC development and identify the underlying molecular mechanisms.Methods HOTAIR expression levels in human EC tissues and the corresponding adjacent tissues and human EC Ishikawa cells were determined by quantitative PCR. Ishikawa cells were treated with E2 or estrogen receptor (ER) inhibitor ICI182780, transfected with siHOTAIR oligo, or infected with lentivirus expressing shHOTAIR/shNC, alone or in combinations. The protein expression of polycomb repressive complex 2 (PRC2) was evaluated by western blotting, and cell migration was measured by transwell assays. A xenograft tumorigenic model was established by inoculating control or stable shHOTAIR-infected Ishikawa cells into nude mice and implanting 17β-estradiol release pellets.Results HOTAIR expression was significantly elevated in human EC tissues. E2 exposure markedly increased HOTAIR levels in Ishikawa cells. Notably, E2 increased the protein expression of PRC2 and promoted EC cell migration, which were dependent on HOTAIR expression, as HOTAIR knockdown abolished these effects of E2. Similarly, E2 promoted the in vivo proliferation of grafted Ishikawa cells via upregulated HOTAIR expression in nude mice.Conclusions Human EC tissues highly express HOTAIR, and E2-induced EC progression depends on HOTAIR expression. This work suggests that the E2-HOTAIR axis is a potential therapeutic target in EC therapy.
Databáze: Directory of Open Access Journals
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