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 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials 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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CiteScore
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