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miR-26a-5p 通过靶向 EP300 发挥作用,EP300 是已知在结直肠癌 CD8⁺ TIL(肿瘤浸润淋巴细胞)中激活 PI3K/AKT/mTOR 信号通路的分子

英文原题:MiR-26a-5p exerts its influence by targeting EP300, a molecule known for its role in activating the PI3K/AKT/mTOR signaling pathway in CD8+tumor-infiltrating lymphocytes of colorectal cancer.

查看英文原题

MiR-26a-5p exerts its influence by targeting EP300, a molecule known for its role in activating the PI3K/AKT/mTOR signaling pathway in CD8+tumor-infiltrating lymphocytes of colorectal cancer.

PubMed 2023/11/30(内容时间) Cell Mol Biol (Noisy-le-grand)

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中文摘要

手术切除仍是结直肠癌的主要治疗方法,而结直肠癌是常见的消化系统恶性肿瘤。近年来,TIL(肿瘤浸润淋巴细胞)疗法已成为肿瘤免疫治疗领域的重要研究方向,有望作为结直肠癌的辅助治疗。

本研究使用单细胞测序数据,评估miR-26a-5p在健康结肠组织、结直肠癌组织及癌旁组织中的表达水平。结果显示,与正常T淋巴细胞相比,肿瘤浸润T淋巴细胞中miR-26a-5p表达相对较低,提示其可能参与调节肿瘤浸润T淋巴细胞功能。尽管既往证据表明miR-26a-5p能够促进癌细胞发育和进展,但其在肿瘤浸润T淋巴细胞中的作用研究有限。实验结果表明,miR-26a-5p抑制PI3K/AKT/mTOR(PAM)信号通路,从而降低CD8+肿瘤浸润细胞清除肿瘤的能力。

我们利用生物信息学预测方法,确定EP300是miR-26a-5p靶向的特定基因。后续研究发现,下调EP300可抵消miR-26a-5p对PAM信号通路激活的抑制作用,同时也会降低CD8+TIL(肿瘤浸润淋巴细胞)的活力和细胞毒性。

因此,miR-26a-5p是有效调控TIL疗法的一个有吸引力的候选靶点。

展开英文摘要原文

Surgical resection remains the primary approach for treating colorectal cancer, which is among the prevalent types of cancers affecting the digestive system. Tumor-infiltrating lymphocyte (TIL) therapy has emerged as a prominent area of study in the field of tumor immunotherapy in recent times, with the potential to serve as a supplementary treatment for colorectal cancer. For this investigation, we employed single-cell sequencing data to assess the manifestation extent of miR-26a-5p exists in healthy colon tissue, tissue affected by colorectal cancer, and tissue adjacent to the tumor. According to our findings, tumor-infiltrating T lymphocytes express comparatively less miR-26a-5p in comparison to normal T lymphocytes, the role of it in modulating the function of tumor-infiltrating T lymphocytes is suggested.

Studies on miR-26a-5p's involvement in tumor-infiltrating T lymphocytes is limited, despite previous evidence indicating its ability to facilitate the development and advancement of cancerous cells. As a result of our experiments, we concluded that miR-26a-5p hindered the PI3K/AKT/mTOR(PAM) signaling pathway, reducing the ability of CD8+ tumor-infiltrating cells eradicate tumors.

Using bioinformatics tools, we utilized prediction methods to identify EP300 as the specific gene targeted by miR-26a-5p. Subsequent research understood that downregulation of EP300 counteracted the suppressive impact exerted by miR-26a-5p on the stimulation of PAM signaling pathway, while it also diminishes the viability and cytotoxicity of CD8+ tumor-infiltrating lymphocytes.

Therefore, miR-26a-5p emerges as a compelling option for the effective control of TIL therapy.

论文信息

作者
Wang C、Lin H、Zhao W、Liang Y、Chen Y、Wang C
第一作者单位
Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, China. wang15940192769@163.com.China
通讯作者单位
Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, China. wcmdyyy@163.com.China
期刊
Cellular and molecular biology (Noisy-le-Grand, France)2023 Nov 30
原文标识
PubMed 38063089 · DOI 10.14715/cmb/2023.69.12.37