Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Cadre Health Care Special Clinic, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Int J Mol Med. 2021 Jan;47(1):374-386. doi: 10.3892/ijmm.2020.4796. Epub 2020 Nov 23.
Sphingosine kinase1 (SphK1) is an oncogenic enzyme that regulates tumor cell apoptosis, proliferation and survival. SphK1 has been reported to promote the development of non‑small cell lung cancer (NSCLC), although the underlying mechanism remains to be determined. The aim of the present study was to examine the expression and function of SphK1 in NSCLC and to explore the underlying molecular mechanism. The results of the present study demonstrated that SphK1 expression was upregulated in NSCLC tissues and cell lines. Overexpression of SphK1 increased the proliferation and migration of NSCLC cells. Additionally, overexpression of SphK1 induced expression of antiapoptotic and migration‑associated genes, such as Bcl‑2, matrix metallopeptidase 2 and cyclin D1. Of note, signal transducer and activator of transcription 3 (STAT3) was also activated in the SphK1‑overexpressing cells. By treatment with a STAT3 inhibitor, it was demonstrated that the SphK1‑induced changes in expression of target genes, as well as the increase in proliferation and migration of NSCLC cells were mediated by STAT3. In conclusion, the effects of SphK1 overexpression on the development of NSCLC were demonstrated to be mediated by the activation of STAT3. These results suggested that inhibition of the SphK1‑STAT3 axis may be a potential strategy for the treatment of NSCLC.
鞘氨醇激酶 1（SphK1）是一种致癌酶，可调节肿瘤细胞凋亡、增殖和存活。有报道称 SphK1 可促进非小细胞肺癌（NSCLC）的发展，但其潜在机制尚待确定。本研究旨在研究 SphK1 在 NSCLC 中的表达和功能，并探讨其潜在的分子机制。本研究结果表明，SphK1 在 NSCLC 组织和细胞系中表达上调。SphK1 的过表达增加了 NSCLC 细胞的增殖和迁移。此外，SphK1 的过表达诱导了抗凋亡和迁移相关基因的表达，如 Bcl-2、基质金属蛋白酶 2 和细胞周期蛋白 D1。值得注意的是，STAT3 在 SphK1 过表达的细胞中也被激活。通过用 STAT3 抑制剂处理，表明 SphK1 诱导的靶基因表达变化以及 NSCLC 细胞增殖和迁移的增加是由 STAT3 介导的。综上所述，SphK1 过表达对 NSCLC 发展的影响是通过激活 STAT3 介导的。这些结果表明，抑制 SphK1-STAT3 轴可能是治疗 NSCLC 的一种潜在策略。
