LncRNA ABHD11-AS1 通过阻止 FUS 介导的 ABHD11 mRNA 降解,激活表皮生长因子受体信号转导,从而促进宫颈癌的进展。

IF 3.4 3区 生物学 Q3 CELL BIOLOGY
Cell Cycle Pub Date : 2023-12-01 Epub Date: 2023-12-26 DOI:10.1080/15384101.2023.2297591
Ting Yang, Sijuan Tian, Juan Zhao, Meili Pei, Minyi Zhao, Xiaofeng Yang
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引用次数: 0

摘要

宫颈癌是最常见的妇科癌症之一,转移率高,预后差,常规化疗效果不佳。长非编码 RNA(lncRNA)ABHD11 反义 RNA 1(ABHD11-AS1)在肿瘤发生中起着重要作用,参与细胞增殖、分化和凋亡。特别是对于宫颈癌而言,ABHD11-AS1的功能和机制仍未确定。本研究探讨了 ABHD11-AS1 在宫颈癌中的作用及其内在机制。我们发现 ABHD11-AS1 在宫颈癌组织中高表达。ABHD11-AS1 和表皮生长因子受体(EGFR)的作用通过对 SiHa 和 Hela 细胞的功能缺失分析和细胞可移动性进行了研究。通过上调p21和Bax,下调细胞周期蛋白D1、Bcl2、MMP9和Vimentin,敲除ABHD11-AS1和表皮生长因子受体能显著抑制SiHa和Hela细胞的增殖、迁移和侵袭,促进细胞凋亡。ABHD11-AS1 基因敲除可降低表皮生长因子受体的表达。此外,ABHD11-AS1 还能调节表皮生长因子受体信号通路,包括 p-EGFR、p-AKT 和 p-ERK。Spearman相关性分析和细胞实验表明,ABHD11在肿瘤组织中高表达,部分抵消了shABHD11-AS1对SiHa和Hela细胞增殖、迁移和侵袭的影响。然后,利用 RNA pulldown 方法确定 ABHD11-AS1 和 FUS 的作用机制。ABHD11-AS1通过与FUS结合抑制了ABHD11 mRNA的降解。为了研究ABHD11-AS1在肿瘤组织中的作用,我们建立了SiHa细胞皮下异种移植。敲除ABHD11-AS1可抑制肿瘤生长并缩小肿瘤体积。ABHD11-AS1敲除抑制了Ki67和Vimentin的表达,并上调了Tunel的表达。我们的数据表明,ABHD11-AS1通过激活表皮生长因子受体信号,阻止FUS介导的ABHD11 mRNA降解,从而促进了宫颈癌的进展。我们的研究结果为lncRNA在宫颈癌治疗中的潜在作用提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
LncRNA ABHD11-AS1 activates EGFR signaling to promote cervical cancer progression by preventing FUS-mediated degradation of ABHD11 mRNA.

Cervical cancer is one of the most common gynecological cancers with high metastasis, poor prognosis and conventional chemotherapy. The long non-coding RNA (lncRNA) ABHD11 antisense RNA 1 (ABHD11-AS1) plays a vital role in tumorigenesis and is involved in cell proliferation, differentiation, and apoptosis. Especially for cervical cancer, the functions and mechanisms of ABHD11-AS1 are still undetermined. In this study, we explored the role and underlying mechanism of ABHD11-AS1 in cervical cancer. We found that ABHD11-AS1 is highly expressed in cervical cancer tissue. The roles of ABHD11-AS1 and EGFR have investigated the loss of function analysis and cell movability in SiHa and Hela cells. Knockdown of ABHD11-AS1 and EGFR significantly inhibited the proliferation, migration, and invasion and promoted apoptosis of SiHa and Hela cells by up-regulating p21 and Bax and down-regulating cyclin D1, Bcl2, MMP9, and Vimentin. ABHD11-AS1 knockdown could decrease the expression of EGFR. In addition, ABHD11-AS1 could regulate the EGFR signaling pathway, including p-EGFR, p-AKT, and p-ERK. Spearman's correlation analysis and cell experiments demonstrated that ABHD11 was highly expressed in tumor tissue and partially offset the effect of shABHD11-AS1 on the proliferation, migration, and invasion of SiHa and Hela cells. Then, RNA pulldown was used to ascertain the mechanisms of ABHD11-AS1 and FUS. ABHD11-AS1 inhibited ABHD11 mRNA degradation by bounding to FUS. A subcutaneous xenograft of SiHa cells was established to investigate the effect of ABHD11-AS1 in tumor tissue. Knockdown of ABDH11-AS1 inhibited tumor growth and decreased the tumor volume. ABHD11-AS1 knockdown inhibited the expression of Ki67 and Vimentin and up-regulated the expression of Tunel. Our data indicated that ABHD11-AS1 promoted cervical cancer progression by activating EGFR signaling, preventing FUS-mediated degradation of ABHD11 mRNA. Our findings provide novel insights into the potential role of lncRNA in cervical cancer therapy.

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来源期刊
Cell Cycle
Cell Cycle 生物-细胞生物学
CiteScore
7.70
自引率
2.30%
发文量
281
审稿时长
1 months
期刊介绍: Cell Cycle is a bi-weekly peer-reviewed journal of high priority research from all areas of cell biology. Cell Cycle covers all topics from yeast to man, from DNA to function, from development to aging, from stem cells to cell senescence, from metabolism to cell death, from cancer to neurobiology, from molecular biology to therapeutics. Our goal is fast publication of outstanding research.
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