MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless
MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless
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MicroRNA-708 通过负靶向 Timeless 抑制细胞增殖并增强宫颈癌细胞对 cDDP 的化学敏感性
DOI：
10.2147/ott.s227015
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发表时间：
2020-01
影响因子：
4
通讯作者：
Jinhua Zhou
中科院分区：
文献类型：
--
作者：
Xinwei Zou;Chenjie Zhu;Lin Zhang;Yi Zhang;Fengqing Fu;Youguo Chen;Jinhua Zhou
目的 宫颈癌是全球女性癌症相关死亡的第四大常见原因。先前的研究报道，microRNA (miRNA) 通过调节基因表达参与癌症进展的多个生物学方面。在这里，我们研究了 microRNA-708 (miR-708) 在宫颈癌中的作用。方法采用定量聚合酶链反应（qPCR）检测宫颈癌组织及配对正常宫颈组织中miR-708的表达水平。通过生物信息学方法、双荧光素酶报告基因测定和蛋白质印迹法鉴定了 miR-708 和 Timeless 之间的相互作用。通过细胞计数试剂盒8（CCK-8）和集落形成实验测定miR-708过表达对细胞增殖和顺铂敏感性的影响。通过流式细胞术分析细胞周期和凋亡。通过彗星试验测定 miR-708 过度表达诱导的 DNA 损伤。通过蛋白质印迹分析参与 DNA 损伤修复的基因的表达水平。结果 与配对的正常宫颈组织相比，miR-708 在宫颈癌组织中表达下调。通过生物信息学方法、Western blotting和双荧光素酶报告基因检测，我们发现Timeless是miR-708的直接靶点。此外，miR-708 抑制细胞活力、集落形成、促进细胞凋亡并诱导 DNA 损伤水平。 MiR-708 还通过损害 ATR/CHK1 信号通路增强宫颈癌细胞对 cDDP 的化疗敏感性。结论 我们得出结论，miR-708 抑制宫颈癌细胞增殖，促进顺铂疗效，并损害 DNA 修复途径。这些结果表明 miR-708 可能是未来宫颈癌治疗的候选治疗靶点。
Purpose Cervical cancer is the fourth most common cause of cancer-associated mortality in women worldwide. Previous studies have reported that microRNAs (miRNAs) are involved in multiple biological aspects of cancer progression by regulating gene expression. Here, we investigated the role of microRNA-708 (miR-708) in cervical cancer. Methods The expression levels of miR-708 in cervical cancer tissues and paired-normal cervical tissues were tested by quantitative polymerase chain reaction (qPCR). The interaction between miR-708 and Timeless was identified by bioinformatics method, dual-luciferase reporter assay, and Western blotting. The effects of over-expression of miR-708 on cell proliferation and cisplatin sensitivity were determined by Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle and apoptosis were analyzed by flow cytometry. DNA damage induced by over-expression of miR-708 was determined by comet assay. Expression levels of the genes involved in repair of DNA damage were analyzed by Western blotting. Results MiR-708 was down-regulated in cervical cancer tissues compared with paired-normal cervical tissues. By bioinformatics method, Western blotting, and dual-luciferase reporter assay, we found that Timeless was a direct target of miR-708. Furthermore, miR-708 suppressed cellular viability, colony formation, promoted apoptosis, and induced DNA damage levels. MiR-708 also enhanced chemosensitivity of cervical cancer cells to cDDP via impairing the ATR/CHK1 signaling pathway. Conclusion We conclude that miR-708 suppresses cell proliferation, facilitates cisplatin efficacy, and impairs DNA repair pathway in cervical cancer cells. These results demonstrate that miR-708 might be a candidate therapeutic target for future cervical cancer therapy.
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影响因子：
--
作者：
Wiegmans AP;Al-Ejeh F;Chee N;Yap PY;Gorski JJ;Da Silva L;Bolderson E;Chenevix-Trench G;Anderson R;Simpson PT;Lakhani SR;Khanna KK
通讯作者：
Khanna KK
复制应力和癌症：探戈需要两个。
影响因子：
3.7
作者：
Lecona E;Fernández-Capetillo O
通讯作者：
Fernández-Capetillo O
DOI：
10.1056/nejm199908263410923
发表时间：
1999
期刊：
--
影响因子：
--
作者：
K. Blank
通讯作者：
K. Blank
影响因子：
56.9
作者：
H. Thorp
通讯作者：
H. Thorp
DOI：
--
发表时间：
2010
期刊：
Asian Pacific journal of cancer prevention : APJCP
影响因子：
--
作者：
T. Song;W. Xia;Ningsheng Shao;Xu Zhang;Chun-yang Wang;Yiguang Wu;Jun Dong;W. Cai;
通讯作者：
T. Song;W. Xia;Ningsheng Shao;Xu Zhang;Chun-yang Wang;Yiguang Wu;Jun Dong;W. Cai;