| 李全营,吴大鹏,顾浩,等.miR-885-3p靶向AKT1对结直肠癌细胞HT-29放射敏感性的影响[J].中华放射医学与防护杂志,2018,38(12):899-906.Li Quanying,Wu Dapeng,Gu Hao,et al.miR-885-3p regulates radiosensitivity of colorectal cancer cell HT-29 by targeting AKT1[J].Chin J Radiol Med Prot,2018,38(12):899-906 |
| miR-885-3p靶向AKT1对结直肠癌细胞HT-29放射敏感性的影响 |
| miR-885-3p regulates radiosensitivity of colorectal cancer cell HT-29 by targeting AKT1 |
| 投稿时间：2018-06-28 |
| DOI：10.3760/cma.j.issn.0254-5098.2018.12.004 |
| 中文关键词: 结直肠癌 miR-885-3p 放疗敏感性 AKT1 |
| 英文关键词:Colorectal cancer miR-885-3p Radiosensitivity AKT1 |
| 基金项目:河南省医学科技攻关计划项目（201601029） |
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| 中文摘要: |
| 目的 探究miR-885-3p对结直肠癌细胞HT-29放射敏感性的影响以及作用机制。方法 荧光定量PCR检测经不同剂量（0、2、4、6、8 Gy）X射线照射后HT-29细胞中miR-885-3p的表达量；建立过表达miR-885-3p细胞株，功能试验探讨其对HT-29细胞放射敏感性的影响；生物信息学预测miR-885-3p下游调控的靶基因，双荧光素酶报告基因法进一步验证；上调和下调miR-885-3p表达量探讨miR-885-3p与靶基因丝苏氨酸蛋白激酶1（AKT1）表达量的调控关系；慢病毒转染敲减AKT1表达量，观察其对HT-29细胞放射敏感性的影响；共转染miR-885-3p模拟物，探讨过表达AKT1对miR-885-3p诱导的HT-29细胞放射敏感性的影响。结果 miR-885-3p在放射诱导的HT-29细胞中表达上调（F=46.64，P<0.05）；过表达miR-885-3p和敲减AKT1可通过抑制HT-29细胞存活、促进其凋亡，从而增强HT-29细胞放射敏感性（t=12.33、12.95，P<0.05），放射增敏比（SER）分别为1.602和1.946；抑制miR-885-3p可通过促进HT-29细胞存活、抑制其凋亡从而促进HT-29细胞放射抵抗（t=11.94，P<0.05），SER为0.839；AKT1是miR-885-3p下游靶基因；过表达AKT1反转miR-885-3p增强HT-29放射敏感性的作用，SER为0.680。结论 miR-885-3p通过直接靶向AKT1增加结直肠癌HT-29细胞放射敏感性，为提高临床结直肠癌放疗敏感性提供一个靶点。 |
| 英文摘要: |
| Objective To investigate the effect and mechanism of miR-885-3p on the radiosensitivity of colorectal cancer cell HT-29.Methods The expression of miR-885-3p in HT-29 cells irradiated with different doses (0, 2, 4, 6, 8 Gy) of X-rays was detected by qPCR. The effect of miR-885-3p in modulating cell radiosensitivity was assessed in HT-29 cells with miR-885-3p overexpression. Bioinformatics prediction and dual luciferase reporter gene assay were employed to identify the direct target gene of miR-885-3p. Relationship between miR-885-3p and target gene tyrosine kinase 1 (AKT1) was investigated via regulation of miR-885-3p expression. The effect of AKT1 on radiosensitivity in HT-29 cells was evaluated through knockdown AKT1. The effect of AKT1 on miR-885-3p-induced radiosensitivity was detected by co-transferring miR-885-3p and AKT1 gene into HT-29 cells.Results miR-885-3p expression was up-regulated in radiation-induced HT-29 cells (F=46.64, P<0.05). Over-expression of miR-885-3p and knockdown of AKT1 enhanced cell radiosensitization by inhibiting survival and promoting apoptosis (t=12.33, 12.95, P<0.05) with SER of 1.602 and 1.946, respectively. Inhibition of miR-885-3p promoted radioresistance by increasing cell survival and inhibiting apoptosis (t=11.94, P<0.05) with a SER of 0.839. AKT1 is a target gene downstream of miR-885-3p, overexpression of AKT1 reversed the effect of miR-885-3p on cell radiosensitivity with a SER of 0.680.Conclusions miR-885-3p can enhance the radiosensitivity of colorectal cancer HT-29 cells by directly targeting AKT1, which provides a target for improving the radiosensitivity of clinical colorectal cancer. |
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