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长链非编码 RNA HOTAIR 通过下调转移相关基因抑制宫颈癌的转移。

HOTAIR knockdown impairs metastasis of cervical cancer cells by down-regulating metastasis-related genes.

机构信息

Department of Obstetrics and Gynecology, Daqing Oilfield General Hospital, Daqing, P.R. China.

Department of Oncology, Daqing Oilfield General Hospital and Huiren Cancer Hospital, Daqing, P.R. China.

出版信息

J Obstet Gynaecol. 2023 Dec;43(1):2181060. doi: 10.1080/01443615.2023.2181060.

Abstract

This study investigated the role of LncRNA HOTAIR knockdown in the biological impacts on cervical cancer cells. The HOTAIR gene in two human cervical cancer cell lines was silenced with small interfering (si) RNA siHOTAIR. Proliferation, apoptosis, migration and invasion of cells were assessed following the knockdown. The expressions of Notch1, EpCAM, E-cadherin, vimentin and STAT3 were assessed using qRT-PCR and Western blotting analysis. Compared with controls, HOTAIR levels were reduced significantly, the OD values of cells were significantly decreased in proliferation assays, cell apoptosis was significantly increased, cell migration and invasion were significantly reduced after HOTAIR knockdown. Molecular analysis showed that Notch1, EpCAM, vimentin and STAT3 expressions were decreased significantly, while the expression of E-cadherin was significantly increased after HOTAIR knockdown. Rescue experiments further confirmed that Notch1 and STAT3 were involved in siHOTAIR-mediated reduction of migration and invasion of cervical cancer cells.IMPACT STATEMENT Long non-coding RNAs including HOTAIR, is implicated in occurrence and development of cancer and have been explored to develop new therapeutic options for cancer. HOTAIR silencing significantly reduces the viability and migration ability of cells and induces cell apoptosis, adding experimental data supporting the potential use of HOTAIR specific-siRNA as a therapeutic avenue for the cancer. The finding from this study would help develop clinically applicable therapeutic avenues for the cancer and identify new treatment targets in the relevant pathways leading to new drugs or treatments.

摘要

本研究探讨了 LncRNA HOTAIR 敲低在宫颈癌细胞生物学影响中的作用。用小干扰 (si) RNA siHOTAIR 沉默了两种人宫颈癌细胞系中的 HOTAIR 基因。敲低后评估细胞的增殖、凋亡、迁移和侵袭。使用 qRT-PCR 和 Western blot 分析评估 Notch1、EpCAM、E-钙粘蛋白、波形蛋白和 STAT3 的表达。与对照组相比,HOTAIR 水平显著降低,增殖试验中细胞的 OD 值显著降低,细胞凋亡显著增加,HOTAIR 敲低后细胞迁移和侵袭显著减少。分子分析显示,HOTAIR 敲低后 Notch1、EpCAM、波形蛋白和 STAT3 的表达显著降低,而 E-钙粘蛋白的表达显著增加。挽救实验进一步证实,Notch1 和 STAT3 参与了 siHOTAIR 介导的宫颈癌细胞迁移和侵袭的减少。

意义陈述:包括 HOTAIR 在内的长非编码 RNA 与癌症的发生和发展有关,并已被探索用于开发癌症的新治疗选择。HOTAIR 沉默显著降低细胞活力和迁移能力,并诱导细胞凋亡,为 HOTAIR 特异性-siRNA 作为癌症治疗途径的潜在用途提供了实验数据支持。本研究的发现将有助于为癌症开发临床适用的治疗途径,并确定相关途径中的新治疗靶点,从而开发出新的药物或治疗方法。

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