MicroRNA (miR)-199a-5p has been shown to function as a tumor suppressor in some malignancies but its role in esophageal cancer is poorly understood. To further explore its role in esophageal cancer, we sought to investigate the interaction between miR-199a-5p and Jun-B, an important component of the AP1 transcription factor, which contains a potential binding site for miR-199a-5p in its mRNA. We found that levels of miR-199a-5p are reduced in both human esophageal cancer specimens and in multiple esophageal cancer cell lines compared to esophageal epithelial cells. Jun-B expression is correspondingly elevated in these tumor specimens and in several cell lines compared to esophageal epithelial cells. Jun-B mRNA expression and stability, as well as protein expression, are markedly decreased following miR-199a-5p overexpression. A direct interaction between miR-199a-5p and Jun-B mRNA was confirmed by a biotinylated RNA-pull down assay and luciferase reporter constructs. Either forced expression of miR-199a-5p or Jun-B silencing led to a significant decrease in cellular proliferation as well as in AP-1 promoter activity. Our results provide evidence that miR-199a-5p functions as a tumor suppressor in esophageal cancer cells by regulating cellular proliferation, partially through repression of Jun B.
MicroRNA-199a-5p（miR-199a-5p）已被证实可在多种恶性肿瘤中发挥抑癌作用，但其在食管癌中的作用尚不明确。为深入探究其在食管癌中的功能，本研究旨在探讨miR-199a-5p与AP1转录因子重要组分Jun-B之间的相互作用——Jun-B的mRNA序列中存在miR-199a-5p的潜在结合位点。研究发现，相较于正常食管上皮细胞，人食管癌组织标本及多种食管癌细胞系中miR-199a-5p表达水平显著降低，而Jun-B表达则相应升高。过表达miR-199a-5p可显著降低Jun-B的mRNA表达水平、mRNA稳定性及蛋白表达。通过生物素标记RNA下拉实验和荧光素酶报告基因系统，证实了miR-199a-5p与Jun-B mRNA之间存在直接相互作用。强制表达miR-199a-5p或沉默Jun-B均能显著抑制细胞增殖并降低AP-1启动子活性。本研究证明miR-199a-5p通过部分抑制Jun-B表达调控细胞增殖，从而在食管癌细胞中发挥抑癌作用。
MiR-199a-5p Decreases Esophageal Cancer Cell Proliferation Partially through Repression of Jun-B
肿瘤(癌症)患者之家