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circFOXO3 受 KLF16 诱导通过海绵吸附 miR-29a-3p 和 miR-122-5p 调节肾透明细胞癌细胞生长和自然杀伤细胞细胞毒性活性。

circFOXO3 Induced by KLF16 Modulates Clear Cell Renal Cell Carcinoma Growth and Natural Killer Cell Cytotoxic Activity through Sponging miR-29a-3p and miR-122-5p.

机构信息

Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China.

Nursing Department, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, China.

出版信息

Dis Markers. 2022 Aug 29;2022:6062236. doi: 10.1155/2022/6062236. eCollection 2022.

DOI:10.1155/2022/6062236
PMID:36072902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9444423/
Abstract

Renal cell carcinoma (RCC) is one of the most common urological malignancies with high incidence and metastatic relapse. Clear cell RCC (ccRCC) comprises nearly 70% of all RCC cases and is responsible for the majority of morbidity and mortality of RCC. Due to the poor diagnosis strategy and unsatisfactory clinical intervention, ccRCC causes a huge economic burden and poor patient quality of life; therefore, novel diagnostic or therapeutic targets for ccRCC are urgently needed. This study investigated the biological role of circFOXO3 in ccRCC development, showing that circFOXO3 is highly expressed in RCC cells and tissues and inhibits the viability of ccRCC cells. circFOXO3 dysregulation regulates NK cell cytotoxicity towards RCC cells by directly sponging miR-29a-3p and miR-122-5p. Overexpression of miR-29a-3p or miR-122-5p attenuated NK cell toxicity towards RCC cells and the transcriptional factor Kruppel-Like Factor 16 (KLF16) regulates circFOXO3 expression in RCC cells. In conclusion, this study has partially elucidated the function of circFOXO3 in ccRCC development, providing potential novel therapeutic targets for ccRCC.

摘要

肾细胞癌 (RCC) 是最常见的泌尿系统恶性肿瘤之一,具有较高的发病率和转移性复发率。透明细胞 RCC (ccRCC) 约占所有 RCC 病例的 70%,是 RCC 发病率和死亡率的主要原因。由于诊断策略不佳和临床干预效果不理想,ccRCC 给患者带来了巨大的经济负担和较差的生活质量;因此,迫切需要针对 ccRCC 的新型诊断或治疗靶点。本研究探讨了 circFOXO3 在 ccRCC 发展中的生物学作用,结果表明 circFOXO3 在 RCC 细胞和组织中高表达,并抑制 ccRCC 细胞的活力。circFOXO3 的失调通过直接海绵吸附 miR-29a-3p 和 miR-122-5p 来调节 NK 细胞对 RCC 细胞的细胞毒性。miR-29a-3p 或 miR-122-5p 的过表达减弱了 NK 细胞对 RCC 细胞的毒性,转录因子 Kruppel-Like Factor 16 (KLF16) 调节 RCC 细胞中 circFOXO3 的表达。总之,本研究部分阐明了 circFOXO3 在 ccRCC 发展中的功能,为 ccRCC 提供了潜在的新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2118/9444423/fa0c4b8b6346/DM2022-6062236.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2118/9444423/af79edcc4656/DM2022-6062236.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2118/9444423/fa0c4b8b6346/DM2022-6062236.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2118/9444423/af79edcc4656/DM2022-6062236.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2118/9444423/bda868085d7e/DM2022-6062236.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2118/9444423/4bbbb190cd1b/DM2022-6062236.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2118/9444423/e3d8130c1173/DM2022-6062236.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2118/9444423/a4a195d84bf4/DM2022-6062236.005.jpg
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