LncRNA BCAR4调控JAK2/STAT3信号通路对食管癌细胞侵袭、迁移、炎症和凋亡的影响

LncRNA BCAR4 affects the migration,invasion,inflammation and apoptosis of esophageal cancer cells through regulation of JAK2/STAT3 pathway

目的:探讨长链非编码RNA(lncRNA)乳腺癌抗雌激素抵抗4(BCAR4)介导JAK激酶2/信号转导与转录因子3(JAK2/STAT3)信号通路对食管癌细胞迁移、侵袭、凋亡和炎症因子分泌的影响。方法:采用实时荧光定量PCR(qRT-PCR)法检测BCAR4在食管癌细胞中的表达。在食管癌EC9706细胞中转染BCAR4小干扰RNA(si-BCAR4),Transwell和流式细胞术分别检测细胞迁移、侵袭和凋亡,Western blot法检测白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、磷酸化JAK2(pJAK2)、JAK2、磷酸化STAT3(pSTAT3)、STAT3表达。使用JAK2/STAT3信号通路激活剂Colivelin处理EC9706细胞,观察其在BCAR4沉默诱导的食管癌细胞迁移、侵袭、凋亡和炎症因子表达中的作用。结果:与人正常食管鳞状上皮Het-1A细胞比较,食管癌细胞TE-10、OE19、EC9706中BCAR4表达量明显升高(P<0.05)。沉默BCAR4的表达可明显降低EC9706细胞迁移数、侵袭数以及IL-1β、TNF-α、IL-6、pJAK2和pSTAT3表达,并显著提高细胞凋亡率(P<0.05),而对JAK2、STAT3蛋白水平无显著影响(P>0.05)。激活JAK2/STAT3通路逆转了BCAR4沉默对EC9706细胞迁移、侵袭和炎症因子表达的抑制和对细胞凋亡的诱导。结论:LncRNA BCAR4沉默通过调控JAK2/STAT3信号通路活性,抑制食管癌细胞的迁移、侵袭和炎症因子的分泌,并促进细胞凋亡。

Objective:To investigate the effect of long-chain non-coding RNA(lncRNA)breast cancer anti-estrogen resistance 4(BCAR4)-mediated JAK kinase 2/signal transduction and transcription factor 3(JAK2/STAT3)signal pathway on migration,invasion,apoptosis and inflammation of esophageal cancer cells.Methods:The expression of BCAR4 in esophageal cancer cells was detected by qPCR.BCAR4 small interference RNA(si-BCAR4)was transfected in esophageal cancer EC9706 cells.Cell migration,invasion and apoptosis were detected by Transwell and flow cytometry.The expressions of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),phosphorylated JAK2(pJAK2),JAK2,phosphorylated STAT3(pSTAT3)and STAT3 were detected by Western blot.EC9706 cells were treated with Colivelin,an activator of JAK2/STAT3 signal pathway,and to observe the role of EC9706 cells in migration,invasion,apoptosis and expression of inflammatory factors induced by BCAR4 silencing in esophageal cancer cells.Results:Compared with Het-1A cells of normal esophageal squamous epithelium,the expression of BCAR4 in esophageal cancer cells TE-10,OE19 and EC9706 was significantly increased(P<0.05).BCAR4 silencing significantly decreased the number of migration and invasion,the expression of IL-1β,TNF-α,IL-6,pJAK2 and pSTAT3(P<0.05),and increased the apoptosis rate of EC9706 cells(P<0.05),but had no significant effect on the protein levels of JAK2 and STAT3(P>0.05).Activation of JAK2/STAT3 pathway reversed the inhibition of BCAR4 silence on migration,invasion,and expression of inflammatory factors of EC9706 cell,and the induction of apoptosis.Conclusion:LncRNA BCAR4 silencing can inhibit the migration,invasion and secretion of inflammatory factors and promote apoptosis of esophageal cancer cells by regulating the activity of JAK2/STAT3 signal pathway.