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Published on: September 20, 2024
SphK1 promotes development of non‑small cell lung cancer through activation of STAT3
Yuefeng Ma1, Xin Xing2, Ranran Kong1
1Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Abstract:
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.
Insights
Sphingosine kinase 1 (SphK1) promotes non-small cell lung cancer (NSCLC) by activating signal transducer and activator of transcription 3 (STAT3). Inhibiting the SphK1-STAT3 pathway may offer a new treatment strategy for NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sphingosine kinase 1 (SphK1) is an oncogenic enzyme implicated in tumor progression.
- SphK1's role in non-small cell lung cancer (NSCLC) development and its precise molecular mechanisms require further elucidation.
Purpose of the Study:
- To investigate the expression and function of SphK1 in NSCLC.
- To explore the molecular mechanisms underlying SphK1's role in NSCLC progression.
Main Methods:
- Analysis of SphK1 expression in NSCLC tissues and cell lines.
- Assessment of SphK1 overexpression effects on NSCLC cell proliferation and migration.
- Investigation of SphK1's impact on the expression of key genes (Bcl-2, MMP2, Cyclin D1) and STAT3 activation.
- Utilizing a STAT3 inhibitor to determine the role of STAT3 in SphK1-mediated effects.
Main Results:
- SphK1 expression is significantly upregulated in NSCLC.
- SphK1 overexpression enhances NSCLC cell proliferation and migration.
- SphK1 induces the expression of anti-apoptotic (Bcl-2) and pro-migratory genes (MMP2, Cyclin D1).
- SphK1 activates signal transducer and activator of transcription 3 (STAT3).
- STAT3 mediates the SphK1-induced gene expression changes and cellular behaviors.
Conclusions:
- SphK1 promotes NSCLC development through STAT3 activation.
- The SphK1-STAT3 axis is a critical pathway in NSCLC progression.
- Targeting the SphK1-STAT3 pathway presents a potential therapeutic strategy for NSCLC treatment.
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