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微小RNA-199a-3p通过靶向AK4基因调控食管癌细胞的放射抗性。

The miR-199a-3p regulates the radioresistance of esophageal cancer cells via targeting the AK4 gene.

作者信息

Zang Chunbao, Zhao Fangfang, Hua Lei, Pu Youguang

机构信息

1Department of Radiation Oncology, Anhui Provincial Cancer Hospital, West Branch of the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.

2Department of Cancer Epigenetics Program, Anhui Provincial Cancer Hospital, West Branch of the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui People's Republic of China.

出版信息

Cancer Cell Int. 2018 Nov 16;18:186. doi: 10.1186/s12935-018-0689-6. eCollection 2018.

Abstract

BACKGROUND

MiRNAs was recognized as vital regulators involved in cancer development. Radioresistance remains a major obstacle for effective treatment of cancers. The mechanisms on the miRNA-mediated radioresistance of cancers are still poorly understood. The main subject of this study is to find new miRNA biomarker that regulates the radioresistance of esophageal cancer (EC).

METHODS

The cumulative dose of radiation assays were used to screen the EC radioresistant cell lines. Wound-healing and invasion assays were used to characterize the properties of these cell lines. The following survival fraction experiments were performed to test the effects of miR-199a-3p and AK4 in the radioresistance of EC. In addition, we used the luciferase reporter assays to identify the putative underlying mechanism that relates to the miR-199a-3p regulated radio-resistance.

RESULTS

We found that the AK4 gene is one of the targets of miR-199a-3p, which promotes the radioresistance of EC cells. The following experiments by force reversal of the miR-199a-3p or AK4 levels confirmed the relationship of miR-199a-3p and AK4 with the radioresistance of EC cells. In addition, the activities of several signaling pathway were drastically altered by the forced changes of the miR-199a-3p level in EC cells.

CONCLUSION

Taken together, we found that miR-199a-3p can be potentially used as a biomarker for the EC radioresistance. Moreover, these results provides new insights into the mechanism on the radioresistance of EC cells, and also might guide the clinical therapy of EC.

摘要

背景

微小RNA(miRNAs)被认为是参与癌症发展的重要调节因子。放射抗性仍然是癌症有效治疗的主要障碍。miRNA介导的癌症放射抗性机制仍知之甚少。本研究的主要目的是寻找调节食管癌(EC)放射抗性的新miRNA生物标志物。

方法

采用累积辐射剂量测定法筛选EC放射抗性细胞系。采用伤口愈合和侵袭试验来表征这些细胞系的特性。进行以下存活分数实验以测试miR-199a-3p和AK4对EC放射抗性的影响。此外,我们使用荧光素酶报告基因试验来确定与miR-199a-3p调节的放射抗性相关的潜在机制。

结果

我们发现AK4基因是miR-199a-3p的靶标之一,其促进EC细胞的放射抗性。随后通过强制逆转miR-199a-3p或AK4水平进行的实验证实了miR-199a-3p和AK4与EC细胞放射抗性的关系。此外,EC细胞中miR-199a-3p水平的强制变化极大地改变了几种信号通路的活性。

结论

综上所述,我们发现miR-199a-3p可能潜在地用作EC放射抗性的生物标志物。此外,这些结果为EC细胞放射抗性机制提供了新的见解,也可能指导EC的临床治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb84/6240238/bbb336912693/12935_2018_689_Fig1_HTML.jpg

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