The SOX2/PDIA6 axis mediates aerobic glycolysis to promote stemness in non-small cell lung cancer cells.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-06-01 Epub Date: 2024-03-05 DOI:10.1007/s10863-024-10009-y
Xiaoya Wan, Daiyuan Ma, Guanglin Song, Lina Tang, Xianxue Jiang, Yingguo Tian, Zunli Yi, Chengying Jiang, Yong Jin, Anmu Hu, Yuju Bai
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Abstract

Non-small cell lung cancer (NSCLC) is an aggressive and rapidly expanding lung cancer. Abnormal upregulation or knockdown of PDIA6 expression can predict poor prognosis in various cancers. This study aimed to investigate the biological function of PDIA6 in NSCLC. SOX2 and PDIA6 expression in NSCLC tissues and regulatory relationship between them were analyzed using bioinformatics. GSEA was performed on the enrichment pathway of PDIA6. qRT-PCR was utilized to examine expression of SOX2 and PDIA6 in NSCLC tissues and cells, and dual-luciferase reporter assay and ChIP experiments were performed to validate their regulatory relationship. CCK-8 experiment was conducted to assess cell viability, western blot was to examine levels of stem cell markers and proteins related to aerobic glycolysis pathway in cells. Cell sphere formation assay was used to evaluate efficiency of cell sphere formation. Reagent kits were used to measure glycolysis levels and glycolysis products. High expression of PDIA6 in NSCLC was linked to aerobic glycolysis. Knockdown of PDIA6 reduced cell viability, expression of stem cell surface markers, and cell sphere formation efficiency in NSCLC. Overexpression of PDIA6 could enhance cell viability and promote aerobic glycolysis, but the addition of 2-DG could reverse this result. Bioinformatics predicted the existence of upstream transcription factor SOX2 for PDIA6, and SOX2 was significantly upregulated in NSCLC, and they had a binding relationship. Further experiments revealed that PDIA6 overexpression restored repressive effect of knocking down SOX2 on aerobic glycolysis and cell stemness. This work revealed that the SOX2/PDIA6 axis mediated aerobic glycolysis to promote NSCLC cell stemness, providing new therapeutic strategies for NSCLC.

SOX2/PDIA6轴介导有氧糖酵解,促进非小细胞肺癌细胞的干性。
非小细胞肺癌(NSCLC)是一种侵袭性强、发展迅速的肺癌。PDIA6的异常上调或基因敲除可预测各种癌症的不良预后。本研究旨在探讨PDIA6在NSCLC中的生物学功能。采用生物信息学方法分析了SOX2和PDIA6在NSCLC组织中的表达及其调控关系。利用qRT-PCR检测SOX2和PDIA6在NSCLC组织和细胞中的表达,并通过双荧光素酶报告实验和ChIP实验验证它们之间的调控关系。CCK-8实验评估细胞活力,Western印迹检测细胞中干细胞标志物和有氧糖酵解途径相关蛋白的水平。细胞球形成试验用于评估细胞球形成的效率。试剂盒用于测量糖酵解水平和糖酵解产物。PDIA6在NSCLC中的高表达与有氧糖酵解有关。敲除PDIA6会降低NSCLC的细胞活力、干细胞表面标志物的表达和细胞球形成效率。过表达PDIA6可提高细胞活力并促进有氧糖酵解,但加入2-DG可逆转这一结果。生物信息学预测PDIA6存在上游转录因子SOX2,而SOX2在NSCLC中显著上调,二者存在结合关系。进一步的实验发现,过表达PDIA6可恢复敲除SOX2对有氧糖酵解和细胞干性的抑制作用。这项工作揭示了SOX2/PDIA6轴介导有氧糖酵解促进NSCLC细胞干性,为NSCLC提供了新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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