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PPP1R14D 基因高表达对敲除肺腺癌 DMS53 细胞增殖和凋亡的影响。

Effect of PPP1R14D gene high expression in lung adenocarcinoma knocked out on proliferation and apoptosis of DMS53 cell.

机构信息

Ward 2, Department of Respiratory Medicine, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.

Department of Traditional Chinese Medicine, Jianhua District Hospital of Traditional Chinese Medicine, Qiqihar, 161000, China.

出版信息

Clin Transl Oncol. 2022 Oct;24(10):1914-1923. doi: 10.1007/s12094-022-02842-7. Epub 2022 May 17.

DOI:10.1007/s12094-022-02842-7
Abstract

PURPOSE

Globally, lung cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related mortality. Lung adenocarcinoma (LUAD) is a common subtype of lung cancer and carries a poor prognosis. Treatment outcomes biomarkers in LUAD are critical, and there is currently a paucity of data; therefore, there is a need for novel biomarkers and newer therapeutic targets.

METHODS

Bayesian analysis was used to obtain the whole-genome t value of LUAD. Gene set enrichment analysis (GSEA) was conducted to obtain the normalized enrichment scores (NES) of the whole genome, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed using the Gene Set Analysis Toolkit. Herein, we investigated the PPP1R14D expression level at the protein level in LUAD and the impact of PPP1R14D knockdown on the proliferation and apoptosis of LUAD cells in vitro.

RESULTS

A total of 483 LUAD samples and 59 normal control samples were included, and 904 differentially expressed genes (DEGs) and 504 LUAD-related genes reported in the literature were obtained. The DEGs showed that PPP1R14D was the most significantly up-regulated gene. Western blot of 30 cases of LUAD tissue and adjacent normal tissue also found that PPP1R14D was significantly highly expressed in cancer tissues. Lentivirus-mediated shRNA strategy effectively inhibited PPP1R14D expression in human LUAD cells DMS53, while PPP1R14D knockdown induced apoptosis and cell proliferation in DMS53 cells.

CONCLUSION

Abnormally up-regulated PPP1R14D promotes the survival and proliferation of tumor cells in human LUAD and may serve as a therapeutic and diagnostic target for LUAD.

摘要

目的

在全球范围内,肺癌仍是最常见的癌症类型,也是癌症相关死亡的主要原因。肺腺癌(LUAD)是肺癌的常见亚型,预后较差。LUAD 的治疗结果生物标志物至关重要,但目前数据匮乏,因此需要新型生物标志物和新的治疗靶点。

方法

采用贝叶斯分析方法获取 LUAD 的全基因组 t 值。进行基因集富集分析(GSEA)以获取全基因组的标准化富集分数(NES),并使用基因集分析工具包分析京都基因与基因组百科全书(KEGG)通路。在此,我们研究了 LUAD 中 PPP1R14D 蛋白水平的表达及其敲低对 LUAD 细胞体外增殖和凋亡的影响。

结果

共纳入 483 例 LUAD 样本和 59 例正常对照样本,获得了 904 个差异表达基因(DEGs)和 504 个文献报道的 LUAD 相关基因。DEGs 显示 PPP1R14D 是最显著上调的基因。对 30 例 LUAD 组织和相邻正常组织的 Western blot 也发现 PPP1R14D 在癌组织中显著高表达。慢病毒介导的 shRNA 策略有效地抑制了人 LUAD 细胞 DMS53 中的 PPP1R14D 表达,而 PPP1R14D 敲低诱导了 DMS53 细胞的凋亡和细胞增殖。

结论

异常上调的 PPP1R14D 促进了人 LUAD 中肿瘤细胞的存活和增殖,可能成为 LUAD 的治疗和诊断靶点。

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Oncol Rep. 2020 May;43(5):1437-1450. doi: 10.3892/or.2020.7526. Epub 2020 Feb 28.
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Exp Ther Med. 2020 Apr;19(4):2963-2972. doi: 10.3892/etm.2020.8554. Epub 2020 Feb 26.
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LncRNA WWOX‑AS1 inhibits the proliferation, migration and invasion of osteosarcoma cells.
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Mol Med Rep. 2018 Jul;18(1):779-788. doi: 10.3892/mmr.2018.9058. Epub 2018 May 23.