Department of Pediatric Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, China.
Department of Pediatric Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, China.
Biomed Pharmacother. 2016 Oct;83:508-513. doi: 10.1016/j.biopha.2016.07.010. Epub 2016 Jul 18.
Neuroblastoma (NB) is one of the most common solid tumors in children, many microRNAs regulate progression and development of NB. Here, we found miR-1303 was upregulated in NB cells and tissues, miR-1303 overexpression promoted the proliferation of SH-SY5Y NB cell investigated by MTT assay, colony formation assay and anchorage-independent growth ability assay, while miR-1303 knockdown reduced this effect. mechanism analysis suggested glycogen synthase kinase 3 beta (GSK3β) and secreted frizzled-related protein 1 (SFRP1) were the target of miR-1303, luciferase assay revealed miR-1303 directly bound to the 3'UTR of GSK3β and SFRP1. miR-1303 increased expression of MYC and CyclinD1, and decreased the expression of p21 and p27, and further demonstrated miR-1303 promotes NB proliferation. Moreover, there was a negative correlation between miR-1303 expression and GSK3β and SFRP1 expression in NB tissues, confirming GSK3β and SFRP1 were the targets of miR-1303 in NB tissues. Collectively, our findings suggested miR-1303 promotes NB proliferation by targeting GSK3β and SFRP1, and might be a target for NB therapy.
神经母细胞瘤（NB）是儿童中最常见的实体肿瘤之一，许多 microRNAs 调节 NB 的进展和发育。在这里，我们发现 miR-1303 在 NB 细胞和组织中上调，miR-1303 的过表达通过 MTT 检测、集落形成检测和无锚定生长能力检测促进 SH-SY5Y NB 细胞的增殖，而 miR-1303 的敲低则降低了这种效应。机制分析表明糖原合酶激酶 3β（GSK3β）和分泌卷曲相关蛋白 1（SFRP1）是 miR-1303 的靶标，荧光素酶检测显示 miR-1303 直接结合到 GSK3β 和 SFRP1 的 3'UTR。miR-1303 增加了 MYC 和 CyclinD1 的表达，降低了 p21 和 p27 的表达，进一步表明 miR-1303 促进 NB 增殖。此外，NB 组织中 miR-1303 的表达与 GSK3β 和 SFRP1 的表达呈负相关，证实 GSK3β 和 SFRP1 是 NB 组织中 miR-1303 的靶标。总之，我们的研究结果表明，miR-1303 通过靶向 GSK3β 和 SFRP1 促进 NB 增殖，可能是 NB 治疗的靶点。
