SNHG16 knockdown inhibits tumorigenicity of neuroblastoma in children via miR-15b-5p/PRPS1 axis
SNHG16 knockdown inhibits tumorigenicity of neuroblastoma in children via miR-15b-5p/PRPS1 axis
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DOI：
10.1097/wnr.0000000000001537
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发表时间：
2020-12-09
期刊：
影响因子：
1.7
通讯作者：
Tian, Lidan
中科院分区：
文献类型：
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作者：
Ge, Yirong;Tan, Sihai;Tian, Lidan
神经母细胞瘤是一个重要的问题，在儿童。长链非编码RNA（lncRNA）在神经母细胞瘤的致瘤性中发挥重要作用。然而，lncRNA小核仁RNA宿主基因16（SNHG 16）在神经母细胞瘤致瘤性中的作用和机制仍然知之甚少。收集46例神经母细胞瘤标本和28例正常组织。通过定量逆转录PCR或western blot检测SNHG 16、microRNA-15 b-5 p（miR-15 b-5 p）和磷酸核糖焦磷酸合成酶1（PRPS 1）的水平。通过3-（4，5-二甲基-2-噻唑基）-2，5-二苯基-2-H-溴化四氮唑或流式细胞术测量细胞增殖以及周期分布。通过上皮-间质转化或transwell试验研究细胞转移。通过starBase和双荧光素酶报告基因分析探讨miR-15 b-5 p与SNHG 16或PRPS 1的靶向关系。使用异种移植模型分析SNHG 16在体内神经母细胞瘤中的作用。我们发现SNHG 16和PRPS 1在神经母细胞瘤组织和细胞中的表达增加。SNHG 16基因敲低可抑制细胞增殖，使G 0/G1期细胞增多，S期细胞减少。SNHG 16过表达引起相反的效果。SNHG 16沉默抑制神经母细胞瘤细胞转移。PRPS 1基因敲低抑制细胞增殖和转移，调节细胞周期分布。miR-15 b-5 p被SNHG 16吸收并直接靶向PRPS 1。miR-15 b-5 p敲低或PRPS 1过表达减轻了SNHG 16沉默对细胞周期、增殖和转移的影响。SNHG 16敲减减少异种移植物肿瘤生长。总之，SNHG 16下调通过miR-15 b-5 p/PRPS 1轴调节细胞周期、增殖和转移抑制神经母细胞瘤致瘤性。
Neuroblastoma is an important problem in children. Long noncoding RNAs (lncRNAs) exhibit important roles in tumorigenicity of neuroblastoma. However, the role and mechanism of lncRNA small nucleolar RNA host gene 16 (SNHG16) in neuroblastoma tumorigenicity remain poorly understood. Forty-six neuroblastoma samples and 28 normal tissues were harvested. The levels of SNHG16, microRNA-15b-5p (miR-15b-5p), and phosphoribosyl pyrophosphate synthetase 1 (PRPS1) were detected via quantitative reverse transcription PCR or western blot. Cell proliferation as well as cycle distribution were measured via 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide or flow cytometry. Cell metastasis was investigated via epithelial-mesenchymal transition or transwell assay. The target relationship of miR-15b-5p and SNHG16 or PRPS1 was explored via starBase and dual-luciferase reporter assay. The role of SNHG16 in neuroblastoma in vivo was analyzed using a xenograft model. We found SNHG16 and PRPS1 levels were increased in neuroblastoma tissues and cells. SNHG16 knockdown inhibited cell proliferation, increased the cell cycle distribution at G0/G1 phase, and decreased the cells at S phase. SNHG16 overexpression caused an opposite effect. SNHG16 silence suppressed neuroblastoma cell metastasis. PRPS1 knockdown constrained cell proliferation and metastasis and regulated cell cycle distribution. miR-15b-5p was sponged by SNHG16 and directly targeted PRPS1. miR-15b-5p knockdown or PRPS1 overexpression mitigated the influence of SNHG16 silence on cell cycle, proliferation, and metastasis. SNHG16 knockdown reduced xenograft tumor growth. In conclusion, SNHG16 downregulation suppressed neuroblastoma tumorigenicity by regulating cell cycle, proliferation, and metastasis via miR-15b-5p/PRPS1 axis.