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鉴定分化群分子相关的 microRNAs 作为胃肠道癌症免疫治疗的潜在治疗靶点。

Identification of cluster of differentiation molecule-associated microRNAs as potential therapeutic targets for gastrointestinal cancer immunotherapy.

机构信息

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, PR China.

South Sichuan Institution for Translational Medicine, Luzhou, Sichuan, PR China.

出版信息

Int J Biol Markers. 2021 Jun;36(2):22-32. doi: 10.1177/17246008211005473. Epub 2021 Mar 31.

Abstract

BACKGROUND

Cluster of differentiation molecules are markers of immune cells that have been identified as a potential immunotherapeutic target for cancer treatment. MicroRNAs are small non-coding RNAs that act as tumor suppressors or oncogenes whose importance in diagnosis, prognosis, and treatment of gastric and colorectal cancers has been widely reported. However, their association with cluster of differentiation molecules in gastrointestinal cancers has not been well studied. Therefore, our study aimed to analyze the relationship between microRNAs and cluster of differentiation molecules in gastrointestinal cancers, and to identify cluster of differentiation molecule-associated microRNAs as prognostic biomarkers for gastrointestinal cancer patients.

METHODS

Targetscan, Starbase, DIANA microT, and miRDB were used to investigate microRNA profiles that might be correlated with cluster of differentiation molecules in gastrointestinal cancers. Moreover, The Cancer Genome Atlas data analysis was used to investigate the association between cluster of differentiation molecules and microRNA expression in patients with gastric, colon, rectal, pancreatic, and esophageal cancers. The Kaplan-Meier plotter was used to identify the association between overall survival and cluster of differentiation molecule-associated microRNA expression in gastrointestinal cancer patients.

RESULTS

miR-200a, miR-559, and miR-1236 were negatively associated with CD86, CD81, and CD160, respectively, in almost all types of gastrointestinal cancers, which were further verified in the in vitro studies by transfecting microRNA mimics in gastric cancer, colon cancer, pancreatic, and esophageal cell lines.

CONCLUSION

Our study showed that miR-200a, miR-1236, and miR-559 are identified as cluster of differentiation-associated microRNAs in gastrointestinal cancers, providing a novel perspective to identify new therapeutic targets for cancer immunotherapy in gastrointestinal cancer patients.

摘要

背景

分化群分子是免疫细胞的标志物,已被确定为癌症治疗的潜在免疫治疗靶点。微小 RNA 是作为肿瘤抑制因子或癌基因发挥作用的小非编码 RNA,其在胃癌和结直肠癌的诊断、预后和治疗中的重要性已被广泛报道。然而,它们与胃肠道癌症中分化群分子的关系尚未得到很好的研究。因此,我们的研究旨在分析胃肠道癌症中微小 RNA 与分化群分子的关系,并确定与分化群分子相关的微小 RNA 作为胃肠道癌症患者的预后生物标志物。

方法

使用 Targetscan、Starbase、DIANA microT 和 miRDB 来研究可能与胃肠道癌症中分化群分子相关的微小 RNA 谱。此外,还使用癌症基因组图谱数据分析来研究胃癌、结肠癌、直肠癌、胰腺癌和食管癌患者中分化群分子与微小 RNA 表达之间的关系。使用 Kaplan-Meier 绘图器来确定胃肠道癌症患者总体生存率与分化群分子相关微小 RNA 表达之间的关系。

结果

miR-200a、miR-559 和 miR-1236 分别与 CD86、CD81 和 CD160 呈负相关,几乎在所有类型的胃肠道癌症中均如此,这在胃癌、结肠癌、胰腺癌和食管癌细胞系中转染微小 RNA 模拟物的体外研究中得到了进一步验证。

结论

我们的研究表明,miR-200a、miR-1236 和 miR-559 被鉴定为胃肠道癌症中与分化群相关的微小 RNA,为识别胃肠道癌症患者癌症免疫治疗的新治疗靶点提供了新的视角。

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