Wang Lingling, Liu Ying, Li Haixia, Zhang Cui, Wang Hongbo, Dai Shaochun, Cheng Wen, Sun Yan, Zheng Xiulan
Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081 Heilongjiang Province, China.
Department of Computed Tomography, The First Hospital of Harbin, Harbin, 150010 Heilongjiang Province, China.
Mol Ther Nucleic Acids. 2020 Dec 3;23:1110-1119. doi: 10.1016/j.omtn.2020.11.024. eCollection 2021 Mar 5.
Ovarian cancer (OC) is a type of cancer with high prevalence and shocking mortality in women around the world. Radioresistance is a major reason for OC relapse. Mounting studies have shown the significant function of dysregulated microRNAs (miRNAs) in cancer progression and the cellular response to irradiation. The present study inquired about the function and mechanism of microRNA () in regulating radiosensitivity of OC cells. Results showed that was downregulated in OC, and a low level indicated a disappointing prognosis for OC patients. Besides, in OC cells exposed to irradiation, the expression of decreased over time. Functionally, the upregulation of retarded OC cell proliferation and sensitized OC cells to irradiation. Mechanistically, targeted and inhibited fused in sarcoma (). Additionally, was upregulated in OC and its expression further elevated in OC cells under irradiation. Furthermore, targeted to inhibit autophagy, therefore sensitizing OC cells to irradiation. Collectively, our study uncovered as a novel radiosensitizer by targeting in OC cells, which may shed a new light on developing targets for treating patients with OC, particularly those with radioresistance.
卵巢癌（OC）是一种在全球女性中具有高发病率和惊人死亡率的癌症类型。放射抗性是OC复发的主要原因。越来越多的研究表明，失调的微小RNA（miRNA）在癌症进展和细胞对辐射的反应中具有重要作用。本研究探讨了微小RNA（）在调节OC细胞放射敏感性中的功能和机制。结果显示，在OC中表达下调，低水平的表明OC患者预后不佳。此外，在接受辐射的OC细胞中，的表达随时间下降。在功能上，的上调抑制了OC细胞增殖并使OC细胞对辐射敏感。机制上，靶向并抑制肉瘤融合蛋白（）。此外，在OC中上调，其表达在接受辐射的OC细胞中进一步升高。此外，靶向以抑制自噬，从而使OC细胞对辐射敏感。总的来说，我们的研究发现通过靶向OC细胞中的作为一种新型放射增敏剂，这可能为开发治疗OC患者，特别是那些具有放射抗性的患者的靶点提供新的思路。
