Shen MingJing, Xu Zhonghua, Jiang Kanqiu, Xu Weihua, Chen Yongbin, Xu ZhongHeng
Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Tumour Biol. 2017 May;39(5):1010428317695948. doi: 10.1177/1010428317695948.
In this study, we evaluated the prognostic potential and functional regulation of human nature antisense, brain-derived neurotrophic factor antisense, in non-small cell lung cancer. Non-small cell lung cancer carcinoma and adjacent non-carcinoma lung tissues were extracted from 151 patients. Their endogenous brain-derived neurotrophic factor antisense expression levels were compared by quantitative reverse transcription polymerase chain reaction. Clinical relevance between endogenous brain-derived neurotrophic factor antisense expression level and patients' clinicopathological variances or overall survival was analyzed. The potential of brain-derived neurotrophic factor antisense being an independent prognostic factor in non-small cell lung cancer was also evaluated. In in vitro non-small cell lung cancer cell lines, brain-derived neurotrophic factor antisense was upregulated through forced overexpression. The effects of brain-derived neurotrophic factor antisense upregulation on non-small cell lung cancer in vitro survival, proliferation, and migration were evaluated by viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and transwell assays. Brain-derived neurotrophic factor antisense is lowly expressed in non-small cell lung cancer carcinoma tissues and further downregulated in late-stage carcinomas. Brain-derived neurotrophic factor antisense downregulation was closely associated with non-small cell lung cancer patients' advanced tumor, lymph node, metastasis stage, and positive status of lymph node metastasis, and confirmed to be an independent prognostic factor for patients' poor overall survival. In non-small cell lung cancer A549 and H226 cell lines, forced overexpression of brain-derived neurotrophic factor antisense did not alter cancer cell viability but had significantly tumor suppressive effect in inhibiting in vitro non-small cell lung cancer proliferation and migration. Endogenous brain-derived neurotrophic factor antisense in non-small cell lung cancer carcinoma could be a potential biomarker for predicting patients' prognosis. Overexpressing brain-derived neurotrophic factor antisense may also have a therapeutic potential in inhibiting non-small cell lung cancer tumor growth.
在本研究中，我们评估了人源性反义脑源性神经营养因子在非小细胞肺癌中的预后潜力和功能调控。从151例患者中提取非小细胞肺癌癌组织及相邻的非癌肺组织。通过定量逆转录聚合酶链反应比较它们内源性脑源性神经营养因子反义表达水平。分析内源性脑源性神经营养因子反义表达水平与患者临床病理差异或总生存期之间的临床相关性。还评估了脑源性神经营养因子反义作为非小细胞肺癌独立预后因素的潜力。在体外非小细胞肺癌细胞系中，通过强制过表达上调脑源性神经营养因子反义。通过活力、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和Transwell实验评估脑源性神经营养因子反义上调对体外非小细胞肺癌生存、增殖和迁移的影响。脑源性神经营养因子反义在非小细胞肺癌癌组织中低表达，在晚期癌组织中进一步下调。脑源性神经营养因子反义下调与非小细胞肺癌患者的肿瘤进展、淋巴结转移分期及淋巴结转移阳性状态密切相关，并被证实是患者总生存期差的独立预后因素。在非小细胞肺癌A549和H226细胞系中，强制过表达脑源性神经营养因子反义并未改变癌细胞活力，但对抑制体外非小细胞肺癌增殖和迁移具有显著的肿瘤抑制作用。非小细胞肺癌癌组织中的内源性脑源性神经营养因子反义可能是预测患者预后的潜在生物标志物。过表达脑源性神经营养因子反义在抑制非小细胞肺癌肿瘤生长方面也可能具有治疗潜力。
