Hsa_circ_0046264 up-regulated BRCA2 to suppress lung cancer through targeting hsa-miR-1245.

Hsa_circ_0046264 up-regulated BRCA2 to suppress lung cancer through targeting hsa-miR-1245.
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Hsa_circ_0046264 通过靶向 hsa-miR-1245 上调 BRCA2 抑制肺癌

DOI:
10.1186/s12931-018-0819-7
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发表时间:
2018-06-11
影响因子:
5.8
通讯作者:
Su X
Su X
中科院分区:
医学2区
文献类型:
--
作者:
Yang L;Wang J;Fan Y;Yu K;Jiao B;Su X

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肺癌一直是世界范围内死亡人数最多的疾病。基因芯片技术的发展为人类进一步了解基因和发现新的环状RNA提供了帮助。本研究旨在探讨hsa_circ_0046264在肺癌中的生物学功能及其分子机制,为肺癌的早期诊断和临床治疗提供参考。利用基因芯片数据筛选出hsa_circ_0046264的差异基因,并通过生物信息学分析找到其下游基因,并通过荧光素酶报告基因检测进行验证。采用QRT-PCR和Western blot分别检测RNA和蛋白水平。RNase R酶切证实了环状RNA的存在。MTT法、流式细胞仪和DNA损伤实验检测细胞活力、侵袭力和凋亡。裸鼠成瘤和免疫组化证实了hsa_circ_0046264在体内的功能。Hsa_circ_0046264和BRCA 2在肺癌组织中表达下调,而miR-1245表达上调。Hsa_circ_0046264通过靶向miR-1245上调BRCA 2,诱导肺癌细胞凋亡,但抑制其增殖和侵袭。Hsa_circ_0046264在体内抑制肿瘤生长。Hsa_circ_0046264是肺癌的抑癌基因。hsa_circ_0046264过表达可通过下调miR-1245上调BRCA 2表达。本文的在线版本(10.1186/s12931-018-0819-7)包含补充材料,可供授权用户使用。
Lung cancer had been leading mounts of deaths worldwide. Advances in genes microarray had helped human further understand genes and identify novel circular RNAs. This study aimed at investigating the biological functions and molecular mechanisms of hsa_circ_0046264 in lung cancer which may be helpful in lung cancer early diagnosis and clinical treatment. Gene microarray data screened the differential gene of hsa_circ_0046264 and its downstream genes were found by bioinformatics analysis and verified by luciferase reporter assay. QRT-PCR and Western blot was used to detect the RNA and protein levels respectively. RNase R digestion confirmed the existences of circular RNA. Cell viability, invasion and apoptosis were determined by MTT assay, flow cytometry and DNA damage assay. Tumor formation in nude mice and immunohistochemistry proved the functions of hsa_circ_0046264 in vivo. Hsa_circ_0046264 and BRCA2 were down-regulated in lung cancer tissues while miR-1245 was up-regulated. Hsa_circ_0046264 induced apoptosis but inhibited proliferation and invasion of lung cancer cells through targeting miR-1245 to up-regulate BRCA2. Hsa_circ_0046264 inhibited the tumor growth in vivo. Hsa_circ_0046264 was a tumor suppressor in lung cancer. Overexpression of hsa_circ_0046264 could up-regulate BRCA2 expression through down-regulating of miR-1245. The online version of this article (10.1186/s12931-018-0819-7) contains supplementary material, which is available to authorized users.
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