COL4A2 enhances thyroid cancer cell proliferation through the AKT pathway.

IF 2 4区医学 Q3 ONCOLOGY

Oncology Research Pub Date : 2024-08-23 eCollection Date: 2024-01-01 DOI:10.32604/or.2024.047382

Liang He, Wei Han, Kai Yue, Xudong Wang

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引用次数: 0

Abstract

Objectives: Thyroid cancer (THCA) is the most common malignant tumor in endocrine system and the incidence has been increasing worldwide. And the number of patients dying from THCA has also gradually risen because the incidence continues to increase, so the mechanisms related to effective targets is necessary to improve the survival. This study was to preliminarily investigate the effects of the COL4A2 gene on the regulation of thyroid cancer (THCA) cell proliferation and the associated pathways.

Methods: Bioinformatics analysis revealed that COL4A2 was closely associated with cancer development. COL4A2 expression in THCA tissues was analyzed using immunohistochemistry, and survival information was determined via Kaplan‒Meier curves. The expression of COL4A2 and AKT pathway-related genes were analyzed using qPCR and western blot analyses. Colony formation as well as CCK-8 assays exhibited the cell proliferation level and cell activity, respectively. Downstream of COL4A2 was identified by Gene set enrichment analysis (GSEA). The effects of the COL4A2 and AKT pathways on THCA tumor growth in vivo were determined using a mouse model.

Results: Bioinformatics analysis exhibited that COL4A2 plays a significant role in cancer and that the AKT pathway is downstream of COL4A2. THCA patients with high COL4A2 expression had shorter recurrence-free survival. Upregulation of COL4A2 gene expression in 2 THCA cell lines promoted tumor cell growth and activity. The use of AKT pathway blockers also restrained the growth and activity of the 2 THCA cell lines. The use of AKT pathway blockers reduced tumor volume and mass and prolonged mouse survival.

Conclusions: COL4A2 can promote the growth as well as development of THCA through the AKT pathway and COL4A2 could be used as a target for THCA.

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COL4A2 通过 AKT 通路促进甲状腺癌细胞增殖

研究目的甲状腺癌（THCA）是内分泌系统中最常见的恶性肿瘤，其发病率在全球范围内呈上升趋势。而由于发病率的持续上升，死于甲状腺癌的患者人数也逐渐增多，因此有必要研究有效靶点的相关机制，以提高患者的生存率。本研究旨在初步探讨 COL4A2 基因对甲状腺癌（THCA）细胞增殖的调控作用及相关通路：生物信息学分析表明，COL4A2与癌症的发生发展密切相关。采用免疫组化方法分析了 COL4A2 在 THCA 组织中的表达，并通过 Kaplan-Meier 曲线确定了存活信息。利用 qPCR 和 Western 印迹分析了 COL4A2 和 AKT 通路相关基因的表达。集落形成和 CCK-8 检测分别显示了细胞增殖水平和细胞活性。通过基因组富集分析（Gene set enrichment analysis，GSEA）确定了 COL4A2 的下游基因。利用小鼠模型测定了COL4A2和AKT通路对THCA肿瘤体内生长的影响：生物信息学分析表明，COL4A2在癌症中起着重要作用，而AKT通路是COL4A2的下游。COL4A2高表达的THCA患者无复发生存期较短。在两种 THCA 细胞系中，COL4A2 基因表达的上调促进了肿瘤细胞的生长和活性。使用 AKT 通路阻断剂也会抑制这两种 THCA 细胞系的生长和活性。使用 AKT 通路阻断剂可减少肿瘤体积和质量，延长小鼠存活时间：结论：COL4A2可通过AKT通路促进THCA的生长和发展，COL4A2可作为THCA的靶点。

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

Oncology Research 医学-肿瘤学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.