Hsa_Circ_0008035 drives immune evasion of gastric cancer via promoting EXT1-mediated nuclear translocation of PKM2

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-07-24 DOI:10.1016/j.tranon.2024.102004

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Abstract

Circular RNAs (circRNAs) have been reported to be associated with the malignant phenotypes of cancer. However, the role and underlying mechanism of hsa_Circ_0008035 in colorectal cancer (CRC) remains unclear. In this study, we elucidated the pivotal role of hsa_circ_0008035 in gastric cancer progression and immune evasion. Elevated hsa_circ_0008035 levels in gastric cancer patient serum correlated positively with disease advancement, including tumor stages and lymph node metastasis. Functional analyses revealed a negative association between hsa_circ_0008035 and CD8+ T cell number and function. Mechanistically, hsa_circ_0008035 encoded the novel protein EXT1–219aa, suppressing EXT1 phosphorylation and expression. Additionally, hsa_circ_0008035 regulated pyruvate metabolism by influencing the nucleus localization of PKM2. The identified EXT1/PKM2 axis further underscored the intricate regulatory mechanisms orchestrated by hsa_circ_0008035 in gastric cancer, offering potential diagnostic and therapeutic implications in the ongoing pursuit of targeted therapies for gastric cancer patients.

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Hsa_Circ_0008035通过促进EXT1介导的PKM2核转位来驱动胃癌的免疫逃避。

据报道，环状 RNA（circRNA）与癌症的恶性表型有关。然而，hsa_Circ_0008035在结直肠癌（CRC）中的作用及其内在机制仍不清楚。本研究阐明了 hsa_circ_0008035 在胃癌进展和免疫逃避中的关键作用。胃癌患者血清中 hsa_circ_0008035 水平的升高与疾病进展（包括肿瘤分期和淋巴结转移）呈正相关。功能分析显示，hsa_circ_0008035与CD8+ T细胞数量和功能呈负相关。从机理上讲，hsa_circ_0008035编码了新蛋白EXT1-219aa，抑制了EXT1的磷酸化和表达。此外，hsa_circ_0008035还通过影响PKM2的细胞核定位来调节丙酮酸代谢。所发现的EXT1/PKM2轴进一步强调了hsa_circ_0008035在胃癌中的复杂调控机制，为胃癌患者正在进行的靶向治疗提供了潜在的诊断和治疗意义。

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

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.