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NPLOC4 是肺鳞状细胞癌的一个潜在靶点和预后不良的标志。

NPLOC4 is a potential target and a poor prognostic signature in lung squamous cell carcinoma.

机构信息

Department of Oncology, General Hospital of Northern Theater Command, Shenyang, 110011, China.

Jinzhou Medical University, Jinzhou, 121001, China.

出版信息

Sci Rep. 2023 Nov 22;13(1):20430. doi: 10.1038/s41598-023-47782-6.

DOI:10.1038/s41598-023-47782-6
PMID:37993584
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10665339/
Abstract

Few prognostic biomarkers exist for lung squamous cell carcinoma (LUSC), which has a poor five-year survival rate. Using bioinformatics, this study evaluated NPLOC4 as a prognostic marker for patients with lung squamous cell carcinoma. Shorter survival periods and tumor growth were linked to high NPLOC4 expression.Disulfiram (DSF) combined with copper (Cu) targets NPLOC4 to achieve antitumor effects in lung squamous cell carcinoma. Thus, we investigated the effects of DSF with Cu in LUSC. Gene-set enrichment analysis identified ubiquitin-mediated proteolysis as the NPLOC4-associated mechanism influencing LUSC prognosis. In SK-MES-1 cell lines, DSF + Cu increased K48-linked ubiquitinated protein expression and apoptosis. This study identified NPLOC4 as a prognostic biomarker and a potential therapeutic target for LUSC.

摘要

目前,针对肺鳞状细胞癌(LUSC)的预后生物标志物还很少,而这种癌症的五年生存率较差。本研究采用生物信息学方法,评估了 NPLOC4 作为肺鳞状细胞癌患者的预后标志物。高 NPLOC4 表达与较短的生存期和肿瘤生长有关。双硫仑(DSF)与铜(Cu)联合靶向 NPLOC4 可在肺鳞状细胞癌中发挥抗肿瘤作用。因此,我们研究了 DSF 联合 Cu 对 LUSC 的影响。基因集富集分析确定泛素介导的蛋白酶体降解是影响 LUSC 预后的与 NPLOC4 相关的机制。在 SK-MES-1 细胞系中,DSF+Cu 增加了 K48 连接的泛素化蛋白表达和细胞凋亡。本研究鉴定了 NPLOC4 作为 LUSC 的预后生物标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/623f363fd576/41598_2023_47782_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/11ae5fbd552c/41598_2023_47782_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/66d5e1f74dd5/41598_2023_47782_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/1a9f19c7c7c1/41598_2023_47782_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/3e80a1cefd41/41598_2023_47782_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/623f363fd576/41598_2023_47782_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/11ae5fbd552c/41598_2023_47782_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/66d5e1f74dd5/41598_2023_47782_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/1a9f19c7c7c1/41598_2023_47782_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/3e80a1cefd41/41598_2023_47782_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e53d/10665339/623f363fd576/41598_2023_47782_Fig5_HTML.jpg

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Cytotoxic effect of disulfiram/copper on human cervical cancer cell lines and LGR5-positive cancer stem-like cells.双硫仑/铜对人宫颈癌系及 LGR5 阳性肿瘤干细胞样细胞的细胞毒性作用。
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Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways.
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Disulfiram/copper induces antitumor activity against gastric cancer cells in vitro and in vivo by inhibiting S6K1 and c-Myc.双硫仑/铜通过抑制S6K1和c-Myc在体外和体内对胃癌细胞诱导抗肿瘤活性。
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Disulfiram Improves the Anti-PD-1 Therapy Efficacy by Regulating PD-L1 Expression Epigenetically Reactivation of IRF7 in Triple Negative Breast Cancer.双硫仑通过表观遗传调控三阴性乳腺癌中IRF7的表达来提高抗PD-1治疗疗效
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