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miR-155/FOXO3a和miR-222/PTEN在大肠癌细胞系获得性放射抗性中的作用

Involvement of miR-155/FOXO3a and miR-222/PTEN in acquired radioresistance of colorectal cancer cell line.

作者信息

Khoshinani Hamed Manoochehri, Afshar Saeid, Pashaki Abdolazim Sedighi, Mahdavinezhad Ali, Nikzad Safora, Najafi Rezvan, Amini Razieh, Gholami Mohammad Hadi, Khoshghadam Alireza, Saidijam Massoud

机构信息

Research Center for Molecular Medicine, Hamedan University of Medical Sciences, Hamadan, Iran.

Mahdieh Radiotherapy and Brachytherapy Charitable Center, Hamadan, Iran.

出版信息

Jpn J Radiol. 2017 Nov;35(11):664-672. doi: 10.1007/s11604-017-0679-y. Epub 2017 Sep 6.

Abstract

PURPOSE

Finding a novel biomarker for determining the radiosensitivity of colorectal cancer (CRC) is critical. The aim of this study is to evaluate the role of two main miRNAs including miR-222 and miR-155 in radiation response of CRC.

MATERIALS AND METHODS

The radioresistant CRC cell lines were established by exposing the HCT 116 cell line to fractional X-ray radiation. SubG1 fraction analysis, MTT and clonogenic assays were applied to evaluate acquired radioresistant cell line radiosensitivity. miR-222/PTEN and miR-155/FOXO3a expressions were detected by RT PCR.

RESULTS

The clonogenic assay and sub-G1fraction analysis indicated that the RR2 sub-line was significantly more resistant than the parental cell line. MiR-222 and miR-155 were significantly upregulated in the radioresistant cell lines compared with the parental cell lines. The PTEN and FOXO3a expressions in the radioresistant cell lines were significantly higher than in the parental line.

CONCLUSION

These observations indicate that miR-222 and miR-155 could induce radiation resistance in colorectal cancer by targeting PTEN and FOXO3a genes, respectively. Therefore, miR-222 and miR-155 can be suggested as good biomarkers of CRC radiation response.

摘要

目的

寻找一种用于确定结直肠癌(CRC)放射敏感性的新型生物标志物至关重要。本研究的目的是评估两种主要的微小RNA(miRNA),即miR - 222和miR - 155在CRC放射反应中的作用。

材料与方法

通过将HCT 116细胞系暴露于分次X射线辐射来建立耐辐射的CRC细胞系。应用亚G1期分数分析、MTT和克隆形成试验来评估获得的耐辐射细胞系的放射敏感性。通过RT - PCR检测miR - 222/PTEN和miR - 155/FOXO3a的表达。

结果

克隆形成试验和亚G1期分数分析表明,RR2亚系比亲代细胞系具有显著更高的抗性。与亲代细胞系相比,耐辐射细胞系中的miR - 222和miR - 155显著上调。耐辐射细胞系中PTEN和FOXO3a的表达明显高于亲代细胞系。

结论

这些观察结果表明,miR - 222和miR - 155可分别通过靶向PTEN和FOXO3a基因诱导结直肠癌的辐射抗性。因此,miR - 222和miR - 155可被认为是CRC放射反应的良好生物标志物。

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