Department of Pediatrics, The Second Hospital of Dalian Medical University, Dalian, China.
College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Cancer Biother Radiopharm. 2024 May;39(4):264-275. doi: 10.1089/cbr.2020.3705. Epub 2021 Jan 22.
Long noncoding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) has been reported to be an oncogene in a variety of cancers. However, the role of SNHG6 and its associated mechanisms in Wilms' tumor progression remain largely unknown. The expression of SNHG6, microRNA-429 (miR-429), and FGF receptor substrates 2 (FRS2) messenger RNA (mRNA) was detected by quantitative real-time polymerase chain reaction. Cell proliferation was analyzed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and plate colony assay. The apoptosis was assessed by flow cytometry. Cell glycolytic metabolism was analyzed through detecting the lactate dehydrogenase activity, glucose uptake, lactate production, and ATP level. The target relationship between miR-429 and SNHG6 or FRS2 was predicted by miRcode or Starbase and then validated by dual-luciferase reporter assay and RNA pull-down assay. Murine xenograft model was established to validate the function of SNHG6 . The level of SNHG6 was elevated in Wilms' tumor tissues and cells, and SNHG6 played an oncogenic role to promote the proliferation and glycolysis and restrain the apoptosis of Wilms' tumor cells. MiR-429 was identified as a target of SNHG6, and miR-429 interference partly reversed the inhibitory effects induced by SNHG6 silencing on the malignant behaviors of Wilms' tumor cells. FRS2 mRNA bound to miR-429 in Wilms' tumor cells. SNHG6 upregulated the expression of FRS2 through acting as a sponge of miR-429. MiR-429-induced influences in Wilms' tumor cells were largely counteracted by the overexpression of FRS2. SNHG6 silencing suppressed the Wilms' tumor growth through miR-429/FRS2 axis . SNHG6 accelerated Wilms' tumor progression through regulating miR-429/FRS2 signaling and .
长链非编码 RNA (lncRNA) 小核仁 RNA 宿主基因 6 (SNHG6) 在多种癌症中被报道为癌基因。然而，SNHG6 的作用及其在威尔姆斯瘤进展中的相关机制在很大程度上仍不清楚。通过实时定量聚合酶链反应检测 SNHG6、微小 RNA-429 (miR-429) 和 FGF 受体底物 2 (FRS2) 信使 RNA (mRNA) 的表达。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐 (MTT) 测定和板集落测定分析细胞增殖。通过流式细胞术评估细胞凋亡。通过检测乳酸脱氢酶活性、葡萄糖摄取、乳酸生成和 ATP 水平分析细胞糖酵解代谢。通过 miRcode 或 Starbase 预测 miR-429 与 SNHG6 或 FRS2 的靶关系，然后通过双荧光素酶报告基因测定和 RNA 下拉测定验证。建立小鼠异种移植模型验证 SNHG6 的功能。在威尔姆斯瘤组织和细胞中升高 SNHG6 水平，SNHG6 发挥致癌作用，促进威尔姆斯瘤细胞增殖和糖酵解，抑制细胞凋亡。miR-429 被鉴定为 SNHG6 的靶标，miR-429 干扰部分逆转了 SNHG6 沉默对威尔姆斯瘤细胞恶性行为的抑制作用。FRS2 mRNA 与威尔姆斯瘤细胞中的 miR-429 结合。SNHG6 通过作为 miR-429 的海绵上调 FRS2 的表达。miR-429 诱导的威尔姆斯瘤细胞的影响在很大程度上被 FRS2 的过表达抵消。SNHG6 沉默通过 miR-429/FRS2 轴抑制威尔姆斯瘤的生长。SNHG6 通过调节 miR-429/FRS2 信号转导加速威尔姆斯瘤的进展。
