Correlation between serum IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients.
Correlation between serum IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients.
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DOI：
10.18632/oncotarget.13042
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发表时间：
2016-12-27
期刊：
影响因子：
--
通讯作者：
Wu C
中科院分区：
文献类型：
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作者：
Wu C;Xu B;Zhou Y;Ji M;Zhang D;Jiang J;Wu C
IL-1β是炎症启动的重要因子，也可促进恶性转化，表明其具有致瘤性。本研究旨在探讨IL-1、β与miR-144-3p之间的相关性及其在慢性阻塞性肺疾病和系统性红斑狼疮患者中的预后价值。LUAD和LUSC患者的IL-1β水平均显著高于健康对照组(P<；0.001)。在两组人群中，IL-1β水平低的患者预后均好于IL-1β水平高的患者(P<；0.001和P=0.010)。在A549细胞中，经IL-1β作用后，miR-144的表达变化最大(4.38倍)。在LUAD患者中，IL-1β与miR-144-3p呈负相关(r=-0.540，P<；0.001)，且高miR-144-3p组预后较好(P=0.003)。临床分期、IL-1β、miR-144-3p是LUAD的独立危险因素。在体外，IL-1β和miR-144-3p拮抗剂可促进细胞增殖，而miR-144-3p模拟物可减弱IL-1β的促增殖作用。采用酶联免疫吸附试验和定量逆转录聚合酶链式反应分别检测129例LUAD、54例LUSC和40例健康献血员的细胞因子和miR-144-3p。此外，还进行了miRNA阵列的miRNA图谱分析。采用TCGA数据库进行验证，并收集随访数据进行预后评估。用四甲基偶氮唑盐比色法和免疫印迹法检测细胞增殖情况。LUAD患者血清IL-1β水平与miR-144-3p水平呈正相关，可能在转录水平影响miR-144-3p。二者均为影响LUAD预后的独立危险因素。此外，IL-1β和miR-144-3p可能参与了LUAD患者炎症促进型肿瘤的发生。
IL-1β is an essential factor of inflammation initiation, and it also promotes malignant transformation, indicating its tumorigenic property. We aimed to investigate the correlation between IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients. The IL-1β level in both LUAD and LUSC patients was significantly higher than that of healthy donors (P < 0.001). In both populations, patients with low IL-1β level had better prognosis than high IL-1β level (P < 0.001 and P = 0.010, respectively). In A549 cells, miR-144 showed the biggest expression change (−4.38 fold) after IL-1β exposure. In LUAD patients, a negative correlation was detected between IL-1β and miR-144-3p (r = –0.540, P < 0.001) and the high miR-144-3p group had better prognosis (P = 0.003), which was validated by TCGA data. Clinical stage, IL-1β and miR-144-3p were independent risk factors in LUAD patients. In vitro, IL-1β and miR-144-3p antagomir could enhance proliferation and miR-144-3p mimics would attenuate the promoting effect of IL-1β. ELISA and qRT-PCR were applied respectively to detected cytokines and miR-144-3p in 129 LUAD, 54 LUSC and 40 healthy donors. Moreover, miRNA array was carried out for miRNA profiling. TCGA database was employed for validation, and follow up data were collected for prognosis evaluation. MTT assay and western-blot were carried out for proliferation evaluation. In LUAD patients, the serum IL-1β level was correlated with miR-144-3p may affect miR-144-3p at transcriptional level. Both of them were independent risk factors for LUAD prognosis. In addition, IL-1β and miR-144-3p might mediate inflammation-promoted tumorigenesis in LUAD patients.