Cao Dongdong, Wu Zhaofu, Yang Rui, Yao Lixia, Huang Jinhong, Ding Yufei, Ruzi Aynisahan, Pan Zemin, Pan Yuanming, Li Dongmei, Gu Wenyi, Zhang Jinli
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.
J Cancer. 2024 Apr 23;15(11):3338-3349. doi: 10.7150/jca.93595. eCollection 2024.
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.
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。