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CircSOX9 通过作为 miR-485-3p 的分子海绵促进鼻咽癌的进展。

CircSOX9 acts as a molecular sponge of miR-485-3p to promote the progression of nasopharyngeal carcinoma.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, People's Republic of China.

出版信息

Aging (Albany NY). 2022 Jun 14;14(11):4914-4926. doi: 10.18632/aging.204127.

Abstract

Circular RNA (circRNA) plays a vital role in the occurrence and development of nasopharyngeal carcinoma (NPC). However, the role of certain specific circRNAs in NPC are still unknown. In this study, collect tumor samples and adjacent normal tissues from clinical NPC patients and detect the expression of circSOX9 by qRT-PCR. Use nucleoplasmic separation analysis, RNase R digestion assay and FISH to detect the characteristics of circSOX9. After knocking down circSOX9, clone formation experiment and transwell assay were used to detect the proliferation and invasion ability of nasopharyngeal carcinoma cells HONE1 and CNE2, and western blot was used to further detect the level of epithelial-mesenchymal transition (EMT). Use the database to screen for possible downstream target genes and verify them with dual-luciferase experiments. Bioinformatics analysis showed that circSOX9 was significantly up-regulated in NPC, and its expression level was positively correlated with the malignant progression of cancer. Data from function gain or loss studies showed that decrease of circSOX9 inhibited the invasion and proliferation of HONE1 and CNE2 cell lines. Further analysis proved that miR-485-3p was the downstream target of circSOX9. The luciferase test showed that by acting as a molecular sponge of miR-485-3p, circSOX9 promotes the proliferation and invasion of NPC cells, while miR-485-3p can target the expression of SOX9. In conclusion, circSOX9 acts as an oncogene in the progression of NPC through miR-485-3p/SOX9, indicating that circSOX9 can be used as a potential therapeutic target and predictive marker for nasopharyngeal carcinoma.

摘要

环状 RNA(circRNA)在鼻咽癌(NPC)的发生和发展中起着至关重要的作用。然而,某些特定的 circRNA 在 NPC 中的作用尚不清楚。在本研究中,从临床 NPC 患者中收集肿瘤样本和相邻正常组织,并通过 qRT-PCR 检测 circSOX9 的表达。使用核质分离分析、RNase R 消化实验和 FISH 检测 circSOX9 的特征。敲低 circSOX9 后,克隆形成实验和 Transwell 检测用于检测鼻咽癌细胞 HONE1 和 CNE2 的增殖和侵袭能力,Western blot 进一步检测上皮-间充质转化(EMT)的水平。使用数据库筛选可能的下游靶基因,并通过双荧光素酶实验进行验证。生物信息学分析表明,circSOX9 在 NPC 中显著上调,其表达水平与癌症的恶性进展呈正相关。功能获得或缺失研究的数据表明,circSOX9 的减少抑制了 HONE1 和 CNE2 细胞系的侵袭和增殖。进一步分析证明,miR-485-3p 是 circSOX9 的下游靶基因。荧光素酶试验表明,circSOX9 通过作为 miR-485-3p 的分子海绵,促进 NPC 细胞的增殖和侵袭,而 miR-485-3p 可以靶向 SOX9 的表达。总之,circSOX9 通过 miR-485-3p/SOX9 在 NPC 的进展中发挥癌基因作用,表明 circSOX9 可以作为鼻咽癌潜在的治疗靶点和预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e0/9217694/5bbbe3cf11aa/aging-14-204127-g001.jpg

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