张千,朱亚宁,周武碧.长链非编码RNA ZFAS1在食管癌中的表达及作用机制研究[J].转化医学杂志,2020,9(6):326-330
长链非编码RNA ZFAS1在食管癌中的表达及作用机制研究
Effects and the underlying mechanism of long non-coding RNA ZFAS1 in esophageal carcinoma
  
DOI:
中文关键词:  长链非编码RNA  ZFAS1  miR-302b-3p  食管癌  作用机制
英文关键词:Long noncoding RNA  ZFAS1  MiR-302b-3p  Esophageal carcinoma  Mechanism
基金项目:
作者单位
张千 南京医科大学附属淮安第一医院病理科 
朱亚宁 南京医科大学附属淮安第一医院病理科 
周武碧 南京医科大学附属淮安第一医院病理科 
摘要点击次数: 122
全文下载次数: 136
中文摘要:
      目的探讨长链非编码RNA锌指结构反义转录本1(zinc finger antisense 1,ZFAS1)在食管癌中的表达及作用机制。方法采用实时荧光定量PCR法分别检测癌旁组织和食管癌组织、正常食管上皮细胞和食管癌细胞的ZFAS1表达水平,通过细胞增殖活性检测、细胞划痕实验及流式细胞仪检测细胞凋亡技术,评价干扰食管癌细胞表达ZFAS1对细胞增殖、迁移及凋亡的影响,采用荧光素酶报告基因验证微小RNA(microRNA,miRNA)miR-302b-3p是ZFAS1的作用靶点,Western蛋白印迹法检测ZFAS1及miR-302b-3p作用下c-Jun氨基末端激酶2(c-Jun N-terminal kinase 2,JNK2)、胰岛素样生长因子1受体(insulin-like growth factor-1 receptor,IGF-1R)、白细胞介素-1受体相关激酶4(interleukin-1 receptor-associated kinase 4,IRAK-4)和上皮细胞激酶(epithelial cell kinase 2,EphA2)蛋白的表达变化。结果与癌旁组织相比,食管癌组织表达ZFAS1水平升高(t=19.40,P<0.001),与正常食管上皮细胞相比,食管癌细胞表达ZFAS1水平增加(t=13.80,P<0.001),通过抑制细胞表达ZFAS1发现,与NC干扰组相比,显著降低ZFAS1干扰组细胞增殖活性(t值分别=2.933,8.568,10.04,均P<0.05,)及迁移能力(t=13.96,P<0.001),且细胞凋亡率升高(t=10.68,P<0.001)。ZFAS1可通过靶向miR-302b-3p调节JNK2、IGF-1R、IRAK4和EphA2蛋白的表达。结论ZFAS1在食管癌组织中表达显著增加,具有促进食管癌细胞增殖、迁移,抑制凋亡的能力,且ZFAS1可通过靶向miR-302b-3p激活JNK2、IGF-1R、IRAK4和EphA2,有望成为治疗食管癌的潜在靶点。
英文摘要:
      ObjectiveTo investigate the expression and functions of ZFAS1 in esophageal carcinoma. MethodsExpression of ZFAS1 was determined from clinical samples and cell lines by qRT-PCR. The effects of ZFAS1 knockdown on proliferation, migration and apoptosis were evaluated by cell counting kit, wound healing assay and flow cytometry assay in vitro. Luciferase reporter gene assay was used to verify that microRNA (miRNA) miR-302b-3p was the target of ZFAS1. The expression changes of c-Jun N-terminal kinase 2 (JNK2), insulin-like growth factor-1 receptor (IGF-1R), interleukin-1 receptor-associated kinase 4 (IRAK-4) and epithelial cell kinase 2 (EphA2) proteins which might be regulated by ZFAS1 and miR-302b-3p were detected by Western blotting assay. ResultsWe found that the LncRNA ZFAS1 was markedly upregulated in esophageal carcinoma tissues (t=19.40, P<0.001) and cells (t=13.80, P<0.001). Furthermore, knockdown of ZFAS1 significantly suppressed cell proliferation (t=2.933, 8.568, 10.04, respectively, all P<0.05) and migration (t=13.96, P<0.001), induced cell apoptosis (t=10.68, P<0.001) in vitro. Besides, ZFAS1 could regulate the expression of JNK2, IGF-1R, IRAK4 and EphA2 proteins by targeting miR-302b-3p. ConclusionZFAS1 is significantly upregulated in esophageal carcinoma tissues and cells. ZFAS1 can activate JNK2, IGF-1R, IRAK4 and EphA2 by targeting miR-302b-3p. ZFAS1 may represent a potential therapeutic target for esophageal cancer intervention.
查看全文  查看/发表评论  下载PDF阅读器
关闭