Wound Repair & Rehabilitation Wuhan Third Hopital (Tongren Hopital of WuHan University), Wuhan, Hubei, China.
Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):8000-8010. doi: 10.26355/eurrev_201909_19016.
Long noncoding RNAs (lncRNAs) have drawn increasing attention due to their critical roles in various diseases, including melanoma. In this study, we aimed to explore the potential roles and underlying mechanisms of Small nucleolar RNA host gene 17 (SNHG17) in the modulation of melanoma progression.
The levels of SNHG17 in melanoma tissues and cells were determined using RT-PCR. The clinical significance of SNHG17 in melanoma patients was analyzed using Chi-square tests, Kaplan-Meier methods, and multivariate assays. MTT assays, transwell assay, and flow cytometry were carried out to explore the biological functions of SNHG17. The biological mechanism underlying up-regulation of SNHG17 was explored using ChIP analysis and luciferase reporter assays. The related proteins of the PI3K-AKT pathway were determined by Western blot.
High expressions of SNHG17 were observed in both melanoma tissues and cells. Up-regulation of SNHG17 in melanoma patients was associated with lymph node metastasis and tumor stage. Survival assays revealed that those patients with high SNHG17 expression had significantly shorter survival time. SNHG17 was also confirmed to be independently associated with overall survival of melanoma patients. Functional studies confirmed that the proliferation, migration, and invasion of melanoma cells were noticeably reduced by the down-regulation of SNHG17. Mechanistically, the up-regulation of SNHG17 was induced by STAT3. We also found that knockdown of SNHG17 resulted in the remarkable diminution in the phosphorylation levels of PI3K and AKT, suggesting that the activity of the PI3K-AKT pathway was suppressed.
STAT3-induced upregulation of SNHG17 contributed to the progression of melanoma by promoting the PI3K-AKT signaling.
长链非编码 RNA（lncRNAs）因其在包括黑色素瘤在内的各种疾病中的关键作用而受到越来越多的关注。在本研究中，我们旨在探讨小核仁 RNA 宿主基因 17（SNHG17）在调节黑色素瘤进展中的潜在作用和潜在机制。
使用 RT-PCR 测定黑色素瘤组织和细胞中的 SNHG17 水平。使用卡方检验、Kaplan-Meier 方法和多变量分析分析 SNHG17 在黑色素瘤患者中的临床意义。MTT 测定、Transwell 测定和流式细胞术用于研究 SNHG17 的生物学功能。使用 ChIP 分析和荧光素酶报告基因测定探索上调 SNHG17 的生物学机制。通过 Western blot 确定 PI3K-AKT 通路的相关蛋白。
在黑色素瘤组织和细胞中均观察到 SNHG17 的高表达。黑色素瘤患者 SNHG17 的上调与淋巴结转移和肿瘤分期有关。生存分析表明，SNHG17 表达较高的患者生存时间明显缩短。SNHG17 也被证实与黑色素瘤患者的总生存时间独立相关。功能研究证实，下调 SNHG17 可显著降低黑色素瘤细胞的增殖、迁移和侵袭能力。机制上，SNHG17 的上调受 STAT3 诱导。我们还发现，敲低 SNHG17 导致 PI3K 和 AKT 的磷酸化水平明显降低，表明 PI3K-AKT 信号通路的活性受到抑制。
STAT3 诱导的 SNHG17 上调通过促进 PI3K-AKT 信号通路促进黑色素瘤的进展。
