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微小RNA-769-3p通过靶向雷帕霉素靶蛋白抑制卡波西肉瘤相关疱疹病毒感染的SH-SY5Y细胞的细胞增殖。

miR-769-3p inhibits cellular proliferation of KSHV-infected SH-SY5Y cells through targeting mTOR.

作者信息

Cao Dongdong, Wu Zhaofu, Yang Rui, Yao Lixia, Huang Jinhong, Ding Yufei, Ruzi Aynisahan, Pan Zemin, Pan Yuanming, Li Dongmei, Gu Wenyi, Zhang Jinli

机构信息

School of medicine, Shihezi University/Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education,832002, Xinjiang, China.

The Affiliated Hospital of Hubei Provincial Government/Hubei Rehabilitation Hospital, 430064, Hubei, China.

出版信息

J Cancer. 2024 Apr 23;15(11):3338-3349. doi: 10.7150/jca.93595. eCollection 2024.

Abstract

The infection by Kaposi's sarcoma-associated herpesvirus (KSHV) is one of the most common causes of death in AIDS patients. Our studies have found that KSHV can infect SH-SY5Y cells (named SK-RG) and mTOR was up-regulated, which results in remarkable enhancement of cell proliferation, migration. But the regulatory role of mTOR in KSHV infected neurons has not yet been fully elucidated. Here, we find that miR-769-3p is decreased in SK-RG cells, which can exert anti-KSHV effect through negatively regulating the expression of mTOR. The knockdown of mTOR or overexpress of miR-769-3p decreased the proliferation, migration ability and cell cycle related protein of SK-RG cells, and the expression of KSHV related genes. In contrast, activating mTOR function by 3BDO treatment weakened the cellular behaviors of miR-769-3p overexpressing cells. Meanwhile, overexpressed miR-769-3p and rapamycin showed a shared inhibition trend in the effects on cell proliferation and motility. Our data indicated that miR-769-3p can inhibit cell proliferation and migration by down regulating mTOR in KSHV infected SH-SY5Y cells, and can be a candidate molecule for anti-KSHV therapy.

摘要

卡波西肉瘤相关疱疹病毒(KSHV)感染是艾滋病患者最常见的死亡原因之一。我们的研究发现,KSHV可感染SH-SY5Y细胞(命名为SK-RG),且mTOR上调,这导致细胞增殖和迁移显著增强。但mTOR在KSHV感染神经元中的调节作用尚未完全阐明。在此,我们发现SK-RG细胞中miR-769-3p减少,其可通过负向调节mTOR的表达发挥抗KSHV作用。敲低mTOR或过表达miR-769-3p可降低SK-RG细胞的增殖、迁移能力及细胞周期相关蛋白,以及KSHV相关基因的表达。相反,用3BDO处理激活mTOR功能会削弱过表达miR-769-3p细胞的细胞行为。同时,过表达的miR-769-3p和雷帕霉素在对细胞增殖和运动的影响上呈现共同的抑制趋势。我们的数据表明,miR-769-3p可通过下调KSHV感染的SH-SY5Y细胞中的mTOR来抑制细胞增殖和迁移,并且可能是抗KSHV治疗的候选分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/988a/11134426/2f4aee7642ec/jcav15p3338g001.jpg

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