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长链非编码RNA APTR通过靶向雌激素受体α激活Wnt/β-连环蛋白信号通路促进子宫肌瘤细胞增殖。

LncRNA APTR Promotes Uterine Leiomyoma Cell Proliferation by Targeting ERα to Activate the Wnt/β-Catenin Pathway.

作者信息

Zhou Weiqiang, Wang Guocheng, Li Bilan, Qu Junjie, Zhang Yongli

机构信息

Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Front Oncol. 2021 Mar 10;11:536346. doi: 10.3389/fonc.2021.536346. eCollection 2021.

DOI:10.3389/fonc.2021.536346
PMID:33777725
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7989393/
Abstract

The molecular mechanisms by which uterine leiomyoma (UL) cells proliferate are unclear. Long noncoding RNA (lncRNA) is reported to participate in the occurrence and development of gynecological cancers. We investigated the molecular mechanisms that lncRNA uses in UL. We found that lncRNA Alu-mediated p21 transcriptional regulator (APTR) showed higher expression in UL tumor tissues compared with that in normal uterine tissues. APTR induced cell proliferation and colony formation both and . The JASPAR database showed that APTR was likely interacted with ERα, and these molecules were identified laser scanning confocal microscopy and RNA immunoprecipitation analysis. To verify the correlation between APTR and ERα, we overexpressed and underexpressed APTR and simultaneously expressed ERα. The results showed that APTR function was suppressed. APTR increased the expressions of the proteins in the Wnt pathway, and inhibiting ERα eliminated these responses. In conclusion, our data suggest that APTR promoted leiomyoma cell proliferation through the Wnt pathway by targeting ERα, suggesting a new role of APTR in the Wnt signaling pathway in UL.

摘要

子宫平滑肌瘤(UL)细胞增殖的分子机制尚不清楚。据报道,长链非编码RNA(lncRNA)参与妇科癌症的发生和发展。我们研究了lncRNA在UL中发挥作用的分子机制。我们发现,与正常子宫组织相比,lncRNA铝介导的p21转录调节因子(APTR)在UL肿瘤组织中表达更高。APTR在体内和体外均诱导细胞增殖和集落形成。JASPAR数据库显示,APTR可能与雌激素受体α(ERα)相互作用,并且通过激光扫描共聚焦显微镜和RNA免疫沉淀分析鉴定了这些分子。为了验证APTR与ERα之间的相关性,我们过表达和低表达APTR,并同时表达ERα。结果显示APTR功能受到抑制。APTR增加了Wnt通路中蛋白质的表达,而抑制ERα消除了这些反应。总之,我们的数据表明,APTR通过靶向ERα促进Wnt通路中的平滑肌瘤细胞增殖,提示APTR在UL的Wnt信号通路中具有新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/ee3304f063ab/fonc-11-536346-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/fdd3da3c9f82/fonc-11-536346-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/d768ff504a2b/fonc-11-536346-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/ba8026bb8933/fonc-11-536346-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/ee3304f063ab/fonc-11-536346-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/fdd3da3c9f82/fonc-11-536346-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/d768ff504a2b/fonc-11-536346-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/ba8026bb8933/fonc-11-536346-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03de/7989393/ee3304f063ab/fonc-11-536346-g004.jpg

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