MiR-199a-5p Decreases Esophageal Cancer Cell Proliferation Partially through Repression of Jun-B.
MiR-199a-5p Decreases Esophageal Cancer Cell Proliferation Partially through Repression of Jun-B.
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DOI：
10.3390/cancers15194811
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发表时间：
2023-09-30
期刊：
影响因子：
5.2
通讯作者：
Donahue, James M.
中科院分区：
文献类型：
--
作者：
Phatak, Pornima;Tulapurkar, Mohan E.;Burrows, Whitney M.;Donahue, James M.
在不同类型的癌症中，特定microRNA的表达可能会发生显着变化。MiR-199 a-5 p已被证明在多种恶性肿瘤中下调，并作为肿瘤抑制因子发挥作用。我们先前已经证明，与食管上皮细胞相比，miR-199 a-5 p在食管鳞状细胞癌细胞系中显著下调。MiR-199 a-5 p被预测与Jun-B mRNA直接相互作用，Jun-B mRNA是AP 1转录因子的重要组分，具有高亲和力。我们研究的目的是确定Jun-B在食管癌细胞中的表达，并研究miR-199 a-5 p和Jun-B在这些细胞中的相互作用，并表征这种相互作用的功能意义。MicroRNA（miR）-199a-5p在某些恶性肿瘤中具有肿瘤抑制作用，但其在食管癌中的作用尚不清楚。为了进一步探索其在食管癌中的作用，我们试图研究miR-199 a-5 p和Jun-B之间的相互作用，Jun-B是AP 1转录因子的重要组成部分，其mRNA中含有miR-199 a-5 p的潜在结合位点。我们发现，与食管上皮细胞相比，miR-199 a-5 p的水平在人食管癌标本和多种食管癌细胞系中均降低。与食管上皮细胞相比，在这些肿瘤标本和几种细胞系中Jun-B表达相应升高。在miR-199 a-5 p过表达后，Jun-B mRNA表达和稳定性以及蛋白质表达显著降低。通过生物素化RNA下拉测定和荧光素酶报告基因构建体证实了miR-199 a-5 p和Jun-B mRNA之间的直接相互作用。miR-199 a-5 p的强制表达或Jun-B沉默导致细胞增殖以及AP-1启动子活性的显著降低。我们的研究结果提供了证据表明，miR-199 a-5 p在食管癌细胞中通过调节细胞增殖，部分通过抑制Jun B发挥肿瘤抑制剂的作用。
The expression of specific microRNAs may be significantly altered in different kinds of cancers. MiR-199a-5p has been shown to be downregulated in multiple malignancies and function as a tumor suppressor. We have previously shown that miR-199a-5p is markedly downregulated in esophageal squamous cancer cell lines compared to esophageal epithelial cells. MiR-199a-5p is predicted to interact directly with Jun-B mRNA, an important component of the AP1 transcription factor, with high affinity. The aim of our study was to determine expression of Jun-B in esophageal cancer cells as well as to investigate the interaction between miR-199a-5p and Jun-B in these cells and to characterize the functional implications of this interaction. 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.
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Project Team: National Institutes of Health
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作者：
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影响因子：
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作者：
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通讯作者：
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