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Reduced interleukin-38 in non-small cell lung cancer is associated with tumour progression.

ABSTRACT: Lung cancer continues to be the leading cause of cancer-related deaths worldwide due to its high incidence, malignant behaviour and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-38 (interleukin-38), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. We first evaluated the IL-38 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by real-time PCR, ELISA (enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-38 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs was assessed. IL-38 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The downregulation of IL-38 was significantly correlated with the results of the American Joint Committee on Cancer stage and degree of differentiation, and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-38 in NSCLC cells suppressed cell migration, invasion, proliferation and colony formation through suppressing ?-catenin. IL-38 inhibited NSCLC formation in a mice model and sensitized the cancer cells to chemotherapy drugs. Our results show that IL-38 plays an inhibitory role in NSCLC development and functions as a novel prognostic indicator and a potential therapeutic target.

SUBMITTER: Wang F

PROVIDER: S-EPMC6223208 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Reduced interleukin-38 in non-small cell lung cancer is associated with tumour progression.

Wang Feng F Zhang Weihua W Wu Tianfeng T Chu Heying H

Open biology 20181031 10

Lung cancer continues to be the leading cause of cancer-related deaths worldwide due to its high incidence, malignant behaviour and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-38 (interleukin-38), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. We first ev ...[more]

PMID: 30381361

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Project description:Objectives: Ring finger protein 38 (RNF38), as an E3 ubiquitin ligase, plays an essential role in multiple biological processes by controlling cell apoptosis, cell cycle and DNA repair, and resides in chromosome 9 (9p13) which is involvement in cancer pathogenesis including lung cancer. However, its function in tumorigenesis remains unclear. Hence, this study set out to investigate the biological function and clinical implications of RNF38 in non-small cell lung cancer (NSCLC). Materials and Methods: Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to detect RNF38 protein and mRNA levels in NSCLC and corresponding paratumor tissues. Tissue microarrays (TMA) analysis of 208 NSCLC cases were used to evaluate the relationship between RNF38 expression and clinical implications. Prognostic value was assessed by Kaplan-Meier analysis and log-rank tests. Wound-healing assays, trans-well assays, colony formation assays and CCK8 were used to assess cell migration, invasion and proliferative ability respectively. The analysis of epithelial-to-mesenchymal transition (EMT) phenotype was carried out by immunofluorescence and western blot. Results: Our data revealed that elevated RNF38 expression were more common in NSCLC tissues than paired normal tissues in both mRNA (2.82 ± 0.29 vs. 1.23 ± 0.13) and protein (2.75 ± 0.09 vs. 1.24 ± 0.02) level. High levels of RNF38 expression were significantly associated with lymph node metastases, higher TNM stages (p=0.011), larger tumor size (p=2.09E-04) and predicted poor prognosis. RNF38 expression was inversely correlated with E-cadherin expression (P= 0.025). Moreover, downregulation of RNF38 impaired the proliferation, metastatic and invasive abilities in NSCLC cells. In addition, aberrant RNF38 expression could modulate the key molecules of EMT. Conclusions: Our results indicate that elevated expression of RNF38 is significantly associated with the proliferation and metastatic capacity of NSCLC cells, and RNF38 overexpression can serve as a biomarker of NSCLC poor prognosis.

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Reduced interleukin-38 in non-small cell lung cancer is associated with tumour progression.

Publications

Reduced interleukin-38 in non-small cell lung cancer is associated with tumour progression.

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