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Published on: March 30, 2019
miRNA-124 down-regulates SOX8 expression and suppresses cell proliferation in non-small cell lung cancer
Chao Xie1, Yunwei Han2, Yi Liu3
1Department of Oncology, Qilu Hospital, Shandong University Jinan 250000, Shandong, China.
Abstract:
Non-small lung cell carcinoma (NSCLC) is a leading lethal disease and a global health burden. The function of the Sex determining region Y (SRY)-related high mobility group box (SOX) family gene in cancer has attracted the attention of more and more scientists recently, yet there are few reports regarding the role of SOX in NSCLC. Our study aimed to investigate the expression of SOX8, a protein belonging to the E group of the SOX family, as well as SOX9, in non-small cell lung cancer (NSCLC) and the relationship of gene expression to clinicopathological factors and prognosis in patients. Immunohistochemical analysis was used to measure the expression of SOX8 in 80 NSCLC and 7 adjacent normal tissues. SOX8 expression was detected as elevated in tumor samples and correlated to tumor size (P < 0.001), lymph node metastasis (P = 0.001), differentiation classification (P = 0.015), and clinical stage (P = 0.013) significantly. Moreover, Kaplan-Meier survival analysis demonstrated that shorter survival time for patients who had higher SOX8 expression (P < 0.001). In addition, our experiments indicate that miRNA-124 functions as a tumor suppressor in NSCLC. We also demonstrate miRNA-124 directly targeted and decreased SOX8 in NSCLC cell lines, suggesting smiRNA-124 may regulate NSCLC cell proliferation via decreasing SOX8 (oncogenicity of biomarker in NSCLC).
Insights
Sex determining region Y (SRY)-related high mobility group box 8 (SOX8) is elevated in non-small cell lung cancer (NSCLC) and linked to poorer prognosis. MiRNA-124 suppresses NSCLC by targeting SOX8, suggesting a new therapeutic avenue.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) presents a significant global health challenge.
- The role of SOX family genes in NSCLC remains underexplored.
- SOX8 and SOX9 are SOX family members with potential implications in cancer.
Purpose of the Study:
- To investigate SOX8 expression in NSCLC tissues.
- To correlate SOX8 expression with clinicopathological factors and patient prognosis.
- To explore the regulatory role of miRNA-124 in NSCLC, specifically its interaction with SOX8.
Main Methods:
- Immunohistochemical analysis of SOX8 expression in 80 NSCLC and 7 normal tissues.
- Statistical analysis to assess correlations between SOX8 expression and clinicopathological variables.
- Kaplan-Meier survival analysis to evaluate the prognostic value of SOX8.
- In vitro experiments in NSCLC cell lines to investigate miRNA-124 targeting of SOX8.
Main Results:
- SOX8 expression was significantly elevated in NSCLC tumor samples compared to normal tissues.
- Increased SOX8 expression correlated with larger tumor size, lymph node metastasis, poor differentiation, and advanced clinical stage.
- Higher SOX8 expression was associated with significantly shorter patient survival.
- miRNA-124 was identified as a tumor suppressor in NSCLC and directly targeted SOX8, reducing its levels in NSCLC cell lines.
Conclusions:
- SOX8 is upregulated in NSCLC and serves as a potential oncoprotein, correlating with adverse clinicopathological features and poor prognosis.
- miRNA-124 acts as a tumor suppressor in NSCLC by directly inhibiting SOX8 expression.
- Targeting the miRNA-124/SOX8 axis may offer a novel therapeutic strategy for NSCLC.
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