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ARNT2 is downregulated and serves as a potential tumor suppressor gene in non-small cell lung cancer
Abstract:
The present study aims to investigate the expression pattern of aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of ARNT2 in 104 NSCLC surgical specimens by immunohistochemistry and then analyzed its clinical significance. Additionally, the role of ARNT2 on the biological properties of the NSCLC line HCC827 was experimentally tested in vitro and in vivo to confirm the clinical observations. We found that the expression level of ARNT2 was significantly higher in normal lung tissues compared with NSCLC tissues (P < 0.01). Overall survival (OS) of patients with a high intratumoral ARNT2 level was significantly longer than survival of those with a low ARNT2 level (P = 0.004). In addition, intratumoral ARNT2 expression was an independent prognostic factors for OS (hazard ratio [HR] = 0.529; P = 0.001). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the ARNT2 overexpression inhibited cell viability, while ARNT2 knockdown promoted cell growth in NSCLC cell lines HCC827 and A549. Annexin V/PI assay showed that ARNT2 overexpression increased cell apoptosis, while ARNT2 knockdown decreased cell apoptosis in HCC827 and A549 cells. Moreover, in vivo study showed that attenuated ARNT2 expression in HCC827 cells greatly promoted tumor growth, while overexpressed ARNT2 remarkably inhibited tumor growth in a HCC827 xenograft model. Taken together, our data demonstrate that ARNT2 might serve as a tumor suppressor in NSCLC progression.
Insights
Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is expressed at lower levels in non-small cell lung cancer (NSCLC) tissues. Higher ARNT2 levels correlate with improved patient survival and suggest ARNT2 acts as a tumor suppressor in NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
- Understanding the molecular mechanisms underlying NSCLC progression is crucial for developing effective therapies.
- The role of aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) in NSCLC pathogenesis is not well-defined.
Purpose of the Study:
- To investigate the expression pattern of ARNT2 protein in human NSCLC.
- To analyze the clinical significance of ARNT2 expression in NSCLC patients.
- To elucidate the functional role of ARNT2 in NSCLC cell behavior and tumor growth.
Main Methods:
- Immunohistochemistry was used to assess ARNT2 expression in 104 NSCLC surgical specimens and normal lung tissues.
- Correlation analysis was performed to evaluate the relationship between ARNT2 levels and clinical parameters, including overall survival (OS).
- In vitro (MTT, Annexin V/PI assays) and in vivo (xenograft model) experiments were conducted using NSCLC cell lines (HCC827, A549) to determine the functional impact of ARNT2 modulation.
Main Results:
- ARNT2 expression was significantly lower in NSCLC tissues compared to normal lung tissues (P < 0.01).
- High intratumoral ARNT2 levels were associated with significantly longer OS (P = 0.004) and identified as an independent prognostic factor (HR = 0.529; P = 0.001).
- ARNT2 overexpression inhibited NSCLC cell viability and promoted apoptosis, while ARNT2 knockdown enhanced cell growth and reduced apoptosis in vitro. In vivo studies confirmed that ARNT2 suppressed tumor growth.
Conclusions:
- ARNT2 exhibits significantly reduced expression in NSCLC.
- Intratumoral ARNT2 expression serves as a favorable prognostic biomarker for overall survival in NSCLC patients.
- ARNT2 functions as a tumor suppressor, inhibiting NSCLC cell proliferation and promoting apoptosis, thus representing a potential therapeutic target.
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