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长非编码 RNA FER1L4 通过 PTEN/AKT/p53 信号通路抑制肺癌细胞增殖并促进细胞凋亡。

Long non‑coding RNA FER1L4 inhibits cell proliferation and promotes cell apoptosis via the PTEN/AKT/p53 signaling pathway in lung cancer.

机构信息

Department of Thoracic Surgery, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu 225001, P.R. China.

Department of Cardiac Macrovascular Center, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu 225001, P.R. China.

出版信息

Oncol Rep. 2021 Jan;45(1):359-367. doi: 10.3892/or.2020.7861. Epub 2020 Nov 19.

Abstract

Long non‑coding RNA Fer‑1‑like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression and apoptosis. However, its clinical significance and biological role in non‑small cell lung cancer (NSCLC) are completely unknown. The purpose of this study was to investigate the expression of lncRNA FER1L4 in plasma and tissues of patients with NSCLC and study the mechanism of proliferation and apoptosis of lung cancer cells. The expression levels of FER1L4 in plasma and tissues of NSCLC patients and cell lines were analyzed via RT‑qPCR. The effects of FER1L4 on cell proliferation, migration and invasion were analyzed by CCK‑8, wound healing and Transwell assays, respectively. The expression levels of related proteins were detected by western blot assay, while cell apoptosis was determined by Hoechst staining and flow cytometry. The results revealed that FER1L4 was significantly downregulated in NSCLC plasma and tissues and lung cancer cell lines compared to corresponding controls. Moreover, a significant decrease of cell proliferation, migration and invasion were observed in FER1L4‑overexpressed cells. FER1L4 could promote phosphatase and tension homolog deleted on chromosome ten (PTEN) and p53 expression, inhibit AKT phosphorylation expression, thus increasing the proportion of apoptotic cells. The present study indicated that FER1L4 may inhibit cell proliferation and promote apoptosis of NSCLC cells via the PTEN/AKT/p53 pathway, which provides a better understanding of the pathogenesis of NSCLC and may provide a novel potential therapeutic target for clinical treatment.

摘要

长链非编码 RNA Fer-1 样蛋白 4(FER1L4)在肿瘤进展和细胞凋亡中发挥着重要的调控作用。然而,其在非小细胞肺癌(NSCLC)中的临床意义和生物学作用尚完全未知。本研究旨在探讨 lncRNA FER1L4 在 NSCLC 患者血浆和组织中的表达,并研究其对肺癌细胞增殖和凋亡的作用机制。通过 RT-qPCR 分析 NSCLC 患者和细胞系中 FER1L4 的表达水平。通过 CCK-8 法、划痕愈合实验和 Transwell 实验分别分析 FER1L4 对细胞增殖、迁移和侵袭的影响。通过 Western blot 检测相关蛋白的表达水平,通过 Hoechst 染色和流式细胞术检测细胞凋亡。结果表明,与相应对照相比,FER1L4 在 NSCLC 血浆和组织以及肺癌细胞系中表达显著下调。此外,在过表达 FER1L4 的细胞中观察到细胞增殖、迁移和侵袭显著减少。FER1L4 可促进磷酸酶和张力蛋白同源物缺失的染色体 10(PTEN)和 p53 的表达,抑制 AKT 磷酸化表达,从而增加凋亡细胞的比例。本研究表明,FER1L4 可能通过 PTEN/AKT/p53 通路抑制 NSCLC 细胞的增殖并促进其凋亡,这为深入了解 NSCLC 的发病机制提供了依据,并可能为临床治疗提供新的潜在治疗靶点。

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