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转录 ITPR3 作为人类胰腺癌的潜在靶点和生物标志物。

Transcriptional ITPR3 as potential targets and biomarkers for human pancreatic cancer.

机构信息

Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin 150086, China.

出版信息

Aging (Albany NY). 2022 May 17;14(10):4425-4444. doi: 10.18632/aging.204080.

Abstract

Inositol 1,4,5-Triphosphate Receptor Family (ITPRs) are necessary intracellular Ca2+-release channel encoders and participate in mammalian cell physiological and pathological processes. Previous studies have suggested that ITPRs participate in tumorigenesis of multiple cancers. Nevertheless, the diverse expression profiles and prognostic significance of three ITPRs in pancreatic cancer have yet to be uncovered. In this work, we examined the expression levels and survival dates of ITPRs in patients with pancreatic cancer. As a result, we identified that ITPR1 and ITPR3 expression levels are significantly elevated in cancerous specimens. Survival data revealed that over-expression of ITPR2 and ITPR3 resulted in unfavourable overall survival and pathological stage. The multivariate Cox logistic regression analysis showed that ITPR3 could be an independent risk factor for PAAD patient survival. Moreover, to investigate how ITPRs work, co-expressed genes, alterations, protein-protein interaction, immune infiltration, methylation, and functional enrichment of ITPRs were also analyzed. Then, we evaluated these findings in clinical samples. Moreover, the gain and loss of function of ITPR3 were also conducted. The electron microscope assay was employed to explore the role of ITPR3 in pancreatic cancer cell lines' endoplasmic reticulum stress. In summary, our findings demonstrated that ITPR3 has the potential to be drug targets and biomarkers for human pancreatic cancer.

摘要

肌醇 1,4,5-三磷酸受体家族(ITPRs)是必需的细胞内 Ca2+释放通道编码器,参与哺乳动物细胞的生理和病理过程。先前的研究表明,ITPRs 参与多种癌症的发生。然而,三种 ITPRs 在胰腺癌中的不同表达谱和预后意义尚未被揭示。在这项工作中,我们研究了 ITPRs 在胰腺癌患者中的表达水平和生存日期。结果表明,ITPR1 和 ITPR3 的表达水平在癌症标本中显著升高。生存数据分析表明,ITPR2 和 ITPR3 的过表达导致总体生存和病理分期不良。多变量 Cox 逻辑回归分析表明,ITPR3 可能是 PAAD 患者生存的独立危险因素。此外,为了研究 ITPRs 的工作机制,还分析了 ITPRs 的共表达基因、改变、蛋白质-蛋白质相互作用、免疫浸润、甲基化和功能富集。然后,我们在临床样本中评估了这些发现。此外,还进行了 ITPR3 的功能增益和功能丧失实验。电子显微镜检测用于探索 ITPR3 在胰腺癌细胞系内质网应激中的作用。总之,我们的研究结果表明,ITPR3 有可能成为人类胰腺癌的药物靶点和生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ba/9186782/c36934ad8e29/aging-14-204080-g001.jpg

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