The nuclear transcription factor RelB functions as an oncogene in human lung adenocarcinoma SPC-A1 cells

被引:9
|
作者
Qin, Hualong [1 ]
Zhou, Jun [2 ]
Xu, Jingjing [2 ]
Cheng, Li [2 ]
Tang, Zaixiang [3 ]
Ma, Haitao [1 ]
Guo, Feng [4 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Dept Thorac Surg, Suzhou, Peoples R China
[2] Soochow Univ, Ctr Clin Lab, Affiliated Hosp 1, Suzhou, Peoples R China
[3] Soochow Univ, Dept Biostat, Med Coll, Suzhou, Peoples R China
[4] Nanjing Med Univ, Dept Oncol, Affiliated Suzhou Hosp, Suzhou 215001, Peoples R China
基金
中国国家自然科学基金;
关键词
RelB; Non-small cell lung cancer; Proliferation; Migration; Irradiation; KAPPA-B PATHWAY; CANCER; EXPRESSION; ACTIVATION; SUBUNIT; REQUIREMENT; SENSITIVITY; RESISTANCE; THERAPY; MURINE;
D O I
10.1186/s12935-018-0580-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Lung cancer is a leading public health issue worldwide. Although therapeutic approaches have improved drastically in the last decades, the prognosis of lung cancer patients remains suboptimal. The canonical nuclear transcription factor kappa B (NF-kappa B) signalling pathway is critical in the carcinogenesis of lung cancer. The non-canonical NF-kappa B signalling pathway (represented by RelB) has attracted increasing attention in the pathogenesis of haematological and epithelial malignancies. However, the function of RelB in non-small cell lung cancer (NSCLC) is still unclear. Recently, high expression of RelB has been detected in NSCLC tissues. We have also demonstrated that RelB expression is an independent prognostic factor in NSCLC patients. Methods: The mRNA and protein expression of RelB in NSCLC tissues were detected by qRT-PCR and IHC assay. The cell growth of SPC-A1 cells was detected in real-time using the x-Celligence system and xenograft tumour assays. The proliferation capability of cells was detected using a CFSE assay. Cell apoptosis was measured using Annexin V/PI staining, cell cycle was analyzed by the cytometry. Cell migration abilities were detected using the x-Celligence system and wound healing assays. The relative amounts of the active and inactive gelatinases MMP-2 and MMP-9 were examined using gelatin zymography experiments. Apoptosis of RelB depletion SPC-A1 cells after ionizing radiation at 8 Gy. The expression of cellular proliferation signal pathway related-proteins were examined by Western blot analysis. Results: The expression of RelB increases in NSCLC tissues. High RelB expression was significantly correlated with advanced-metastatic stage in patients with NSCLC. RelB-silencing inhibits cell growth in vitro and in vivo. We found that RelB affected cell proliferation by regulating AKT phosphorylation. RelB silencing attenuates the migration and invasion abilities of SPC-A1 cells and is likely related to the down regulation of MMP-9 activity and Integrin beta-1 expression. In addition, RelB modulated radiation-induced survival of NSCLC cells predominantly by regulating Bcl-xL expression. Conclusions: Given the involvement of RelB in cell proliferation, migration, invasion, and radio-resistance, RelB functions as an oncogene in NSCLC cells. Our data here shed light on unexplored aspects of RelB in NSCLC.
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页数:13
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