Lu Gaihui, Wu Xiujuan, Zhao Zongfeng, Ding Yuan, Wang Peng, Wu Caoying, Kang Xiaojing, Pu Xiongming
Xinjiang Medical University, Urumqi, Xinjiang, China Dermatological Department, Clinical Medical Research Center, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang, China.
Medicine (Baltimore). 2018 Aug;97(35):e11855. doi: 10.1097/MD.0000000000011855.
In vitro, microRNA-126 (miR-126) inhibits SLK cell proliferation, inhibits the cell cycle, induces cell apoptosis, and reduces cell invasiveness. Double luciferase assays have shown that phosphatidylinositol-3 kinase (PI3K) is the miR-126 target in SLK cells. We aimed to investigate the influence of miR-126 on the phosphate and tension homology deleted on chromosome ten (PTEN)/PI3K/protein kinase B (AKT) pathway members in SLK cells and to determine the expression of these pathway members in Kaposi's sarcoma (KS). The mimic and inhibitor of miR-126 were transfected into SLK cells and PTEN and AKT1 expression was assayed in SLK cells by real-time quantitative PCR and western blotting. PTEN, AKT1, phosphorylated (P)-PTEN, and phosphorylated (P)-AKT expression in KS and paraneoplastic skin were assayed by immunohistochemistry. AKT1 expression was downregulated in SLK cells that overexpressed miR-126, while there was no significant difference in PTEN expression between SLK cells overexpressing miR-126 and those in which its expression was knocked down. PTEN and AKT1 were expressed in KS and paraneoplastic skin but P-AKT was not. Interestingly, P-PTEN was not expressed in paraneoplastic skin but it was expressed in 90% of KS biopsies (P < .05). P-PTEN expression was also significantly higher in visceral than in cutaneous KS (P = .01) and was higher in indoor than in outdoor workers (P = .018). In vitro, miR-126 negatively regulated AKT1 expression but no regulation of PTEN expression was evident. Results indicated that in KS, PTEN is activated and may therefore be a potential therapeutic target for KS. In addition, these results also indicate that sunlight may not be the cause of KS.
在体外，微小RNA-126（miR-126）可抑制SLK细胞增殖，抑制细胞周期，诱导细胞凋亡，并降低细胞侵袭性。双荧光素酶检测表明，磷脂酰肌醇-3激酶（PI3K）是SLK细胞中miR-126的靶标。我们旨在研究miR-126对SLK细胞中第10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）/PI3K/蛋白激酶B（AKT）信号通路成员的影响，并确定这些信号通路成员在卡波西肉瘤（KS）中的表达情况。将miR-126模拟物和抑制剂转染到SLK细胞中，通过实时定量PCR和蛋白质印迹法检测SLK细胞中PTEN和AKT1的表达。通过免疫组织化学检测KS组织和癌旁皮肤组织中PTEN、AKT1、磷酸化（P）-PTEN和磷酸化（P）-AKT的表达。在过表达miR-126的SLK细胞中，AKT1表达下调，而过表达miR-126的SLK细胞与敲低其表达的细胞相比，PTEN表达无显著差异。PTEN和AKT1在KS组织和癌旁皮肤组织中均有表达，但P-AKT未表达。有趣的是，P-PTEN在癌旁皮肤组织中未表达，但在90%的KS活检组织中表达（P<0.05）。P-PTEN在内脏型KS中的表达也显著高于皮肤型KS（P=0.01），且在室内工作者中的表达高于室外工作者（P=0.018）。在体外，miR-126负向调节AKT1表达，但对PTEN表达无明显调节作用。结果表明，在KS中，PTEN被激活，因此可能是KS的潜在治疗靶点。此外，这些结果还表明阳光可能不是KS的病因。
