Regulatory mechanisms and clinical perspectives of miRNA in tumor radiosensitivity.

Regulatory mechanisms and clinical perspectives of miRNA in tumor radiosensitivity.
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miRNA在肿瘤放射敏感性中的调控机制和临床前景。

DOI:
10.1093/carcin/bgs235
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发表时间:
2012-11
期刊:
影响因子:
4.7
通讯作者:
Dong Z
Dong Z
中科院分区:
医学2区
文献类型:
--
作者:
Zhao L;Bode AM;Cao Y;Dong Z

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MicroRNA影响肿瘤发生的多个阶段,通过影响DNA损伤修复、细胞周期检查点、细胞凋亡、放射相关信号转导通路和肿瘤微环境,有效地控制肿瘤的放射敏感性。MiRNA还通过阻断DNA损伤反应中两条重要的非同源末端连接修复和同源重组修复途径,在多个水平上有效地调节肿瘤的放射敏感性。在电离辐射中,它干扰四条与辐射有关的通路,包括PI3-K/Akt、NF-κB、MAPK和β信号通路。此外,当miRNA与多种关键分子相互作用时,包括H2 AX、BRCA1、ATM、DNA-PK、RAD51、Chk1、CDc25A、P53、PLK1、HIF-1和VEGF,可以增强miRNA对辐射敏感性的调节作用。因此,深入了解miRNA在肿瘤放射增敏中的作用机制,有助于寻找新的靶点以提高放射治疗效果,并为开发有效的肿瘤治疗方法提供新的临床视角和见解。
MicroRNA (miRNA) influences carcinogenesis at multiple stages and it can effectively control tumor radiosensitivity by affecting DNA damage repair, cell cycle checkpoint, apoptosis, radio-related signal transduction pathways and tumor microenvironment. MiRNA also efficiently modulates tumor radiosensitivity at multiple levels by blocking the two essential non-homologous end-joining repair and homologous recombination repair pathways in the DNA damage response. It interferes with four radio-related pathways in ionizing radiation, including the PI3-K/Akt, NF-κB, MAPK and TGFβ signaling pathways. Moreover, the regulatory effect of miRNA in radiosensitivity can be enhanced when interacting with various key molecules, including H2AX, BRCA1, ATM, DNA-PK, RAD51, Chk1, Cdc25A, p53, PLK1, HIF-1 and VEGF, which are involved in these processes. Therefore, thoroughly understanding the mechanism of miRNA in tumor radiosensitivity could assist in finding novel targets to improve the radiotherapeutic effects and provide new clinical perspectives and insights for developing effective cancer treatments.
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