4.7 Article

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

Journal

CANCER CELL INTERNATIONAL
Volume 18, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s12935-018-0689-6

Keywords

Esophageal cancer; Radioresistance; miR-199a-3p; AK4; TGF beta signaling pathway

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Funding

  1. Natural Science Foundation of Anhui Province [1608085MH224, 1608085QH214]
  2. Fundamental Research Funds for the Central Universities

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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.

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