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miR-1251-5p过表达通过靶向NPTX2抑制透明细胞肾细胞癌的增殖、迁移和免疫逃逸。

miR-1251-5p Overexpression Inhibits Proliferation, Migration, and Immune Escape in Clear Cell Renal Cell Carcinoma by Targeting NPTX2.

作者信息

Yue Lin, Lin Hualong, Yuan Shaofei, Wu Lili, Chen Guangming, Wang Jiaqi, Feng Jieni

机构信息

School of Nursing, Hunan University of Medicine, Huaihua 418000, China.

Department of Medical Oncology, The Third Affiliated Hospital of Wenzhou Medical University, Rui'an 325200, China.

出版信息

J Oncol. 2022 Mar 10;2022:3058588. doi: 10.1155/2022/3058588. eCollection 2022.

Abstract

BACKGROUND

miR-1251-5p was identified as a tumor suppressor in a variety of malignancies; however, its biological function in clear cell renal cell carcinoma (ccRCC) is unknown.

METHODS

The Cancer Genome Atlas (TCGA) database was used to download expression information, including miR-1251-5p, in 521 ccRCC tissues and 71 ordinary tissues, and bioinformatics was used to explore possible target mRNAs. The relationship between miR-1251-5p, target mRNA activity, and clinical factors was examined. To estimate the biological activity of miR-1251-5p and target mRNA in ccRCC cells, we used MTT, colony formation, enzyme-linked immunosorbent, and Transwell assays. We employed a dual-luciferase reporter assay and a western blot to examine the molecular mechanisms of miR-1251-5p in ccRCC cells. In addition, the expressions of miR-1251-5p and target mRNA were further verified in the GEO database.

RESULTS

Our findings revealed that miR-1251-5p binds with NPTX2's 3'-UTR. In TCGA and GEO datasets, miR-1251-5p activity is found to be lower in ccRCC tissues than that in nearby conventional tissues, although NPTX2 activity is higher. In ccRCC sufferers, miR-1251-5p and NPTX2 act as biomarkers that indicate a bad prognosis. Meanwhile, in miR-1251-5p tissues, NPTX2 expression and multiple clinical variables (survival status, grade, T staging, N staging, M staging, and clinical stage) had significant differences ( < 0.05). Structurally, miR-1251-5p inhibited proliferation, migration, and immune escape of ccRCC cells by targeting NPTX2.

CONCLUSION

Our findings indicate that miR-1251-5p constrained ccRCC cell advancement, migration, and immune evasion via targeting NPTX2, providing novel insights into ccRCC target treatment.

摘要

背景

miR-1251-5p在多种恶性肿瘤中被鉴定为肿瘤抑制因子;然而,其在肾透明细胞癌(ccRCC)中的生物学功能尚不清楚。

方法

利用癌症基因组图谱(TCGA)数据库下载521例ccRCC组织和71例正常组织中包括miR-1251-5p在内的表达信息,并通过生物信息学方法探索可能的靶mRNA。检测miR-1251-5p、靶mRNA活性与临床因素之间的关系。为评估miR-1251-5p和靶mRNA在ccRCC细胞中的生物学活性,我们采用了MTT、集落形成、酶联免疫吸附和Transwell实验。我们采用双荧光素酶报告基因实验和蛋白质印迹法检测miR-1251-5p在ccRCC细胞中的分子机制。此外,在GEO数据库中进一步验证了miR-1251-5p和靶mRNA的表达。

结果

我们的研究结果表明,miR-1251-5p与NPTX2的3'-UTR结合。在TCGA和GEO数据集中,虽然NPTX2活性较高,但发现ccRCC组织中miR-1251-5p活性低于邻近的正常组织。在ccRCC患者中,miR-1251-5p和NPTX2作为不良预后的生物标志物。同时,在miR-1251-5p组织中,NPTX2表达与多个临床变量(生存状态、分级、T分期、N分期、M分期和临床分期)存在显著差异(<0.05)。在结构上,miR-1251-5p通过靶向NPTX2抑制ccRCC细胞的增殖、迁移和免疫逃逸。

结论

我们的研究结果表明,miR-1251-5p通过靶向NPTX2抑制ccRCC细胞的进展、迁移和免疫逃逸,为ccRCC的靶向治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d214/8930236/628ca16a1c8a/JO2022-3058588.001.jpg

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