COL10A1 通过调节胰腺腺癌中的 CD276 促进肿瘤发生。
COL10A1 promotes tumorigenesis by modulating CD276 in pancreatic adenocarcinoma.
机构信息
Department of Hepatobiliary surgery, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515041, China.
Department of pharmacy, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515041, China.
出版信息
BMC Gastroenterol. 2023 Nov 16;23(1):397. doi: 10.1186/s12876-023-03045-2.
BACKGROUND
Pancreatic adenocarcinoma (PAAD) is a lethal malignant tumour. Further study is needed to determine the molecular mechanism and identify novel biomarkers of PAAD.
METHODS
Gene expression data from the GSE62165 microarray were analysed with the online software Morpheus to identify differentially expressed genes (DEGs). The STRING database was used to generate a protein‒protein interaction (PPI) network for these DEGs. Hub genes were identified with Cytoscape. COL10A1 expression in PAAD was analysed via the GEPIA database. COL10A1 expression in pancreatic cancer cell lines was measured by using qRT‒PCR. The LinkedOmics database was utilized to perform survival analysis of pancreatic adenocarcinoma patients grouped based on COL10A1 expression level. CCK-8, wound healing, and Transwell assays were used to study the role of COL10A1 in pancreatic cancer cell viability, migration, and invasion. Differentially expressed genes that were related to COL10A1 in PAAD were analysed via the LinkedOmics portal. After COL10A1 was knocked down, CD276 expression was assessed by western blotting.
RESULTS
COL10A1 was identified as one of the hub genes in PAAD by bioinformatics analysis of the GSE62165 microarray with Morpheus, the STRING database and Cytoscape. GEPIA revealed elevated expression of COL10A1 in PAAD samples vs. normal samples. COL10A1 expression was also increased in pancreatic cancer cells vs. control cells. Survival analysis of PAAD patients via LinkedOmics revealed that high expression of COL10A1 was associated with a poorer prognosis. Knockdown of COL10A1 inhibited the proliferation, migration, and invasion of cells in functional assays. Furthermore, mechanistic studies indicated that CD276 was a target of COL10A1 and that knockdown of COL10A1 decreased CD276 expression. Overexpression of CD276 in cells reversed COL10A1 knockdown-induced repression of proliferation and migration.
CONCLUSIONS
Our research suggests that COL10A1 promotes pancreatic adenocarcinoma tumorigenesis by regulating CD276. This study provides new insight into biomarkers and possible targets for pancreatic cancer treatment.
背景
胰腺导管腺癌（PAAD）是一种致命的恶性肿瘤。需要进一步研究以确定其分子机制并鉴定新的 PAAD 生物标志物。
方法
使用在线软件 Morpheus 对 GSE62165 微阵列的基因表达数据进行分析，以鉴定差异表达基因（DEG）。使用 STRING 数据库为这些 DEG 生成蛋白质-蛋白质相互作用（PPI）网络。使用 Cytoscape 鉴定枢纽基因。通过 GEPIA 数据库分析 PAAD 中的 COL10A1 表达。使用 qRT-PCR 测量胰腺癌细胞系中的 COL10A1 表达。使用 LinkedOmics 数据库对基于 COL10A1 表达水平的胰腺腺癌患者进行生存分析。使用 CCK-8、划痕愈合和 Transwell 测定法研究 COL10A1 在胰腺癌细胞活力、迁移和侵袭中的作用。通过 LinkedOmics 门户分析与 PAAD 中的 COL10A1 相关的差异表达基因。敲低 COL10A1 后，通过 Western blot 评估 CD276 的表达。
结果
通过 Morpheus、STRING 数据库和 Cytoscape 对 GSE62165 微阵列的生物信息学分析，COL10A1 被鉴定为 PAAD 的枢纽基因之一。GEPIA 显示 PAAD 样本与正常样本相比 COL10A1 表达升高。与对照细胞相比，胰腺癌细胞中的 COL10A1 表达也增加。通过 LinkedOmics 对 PAAD 患者进行的生存分析表明，COL10A1 高表达与预后不良相关。功能测定中 COL10A1 的敲低抑制了细胞的增殖、迁移和侵袭。此外，机制研究表明 CD276 是 COL10A1 的靶标，COL10A1 的敲低降低了 CD276 的表达。细胞中 CD276 的过表达逆转了 COL10A1 敲低引起的增殖和迁移抑制。
结论
我们的研究表明，COL10A1 通过调节 CD276 促进胰腺导管腺癌的肿瘤发生。这项研究为胰腺癌的治疗提供了新的生物标志物和潜在靶点。
Zotero 插件