circEPSTI1 as a Prognostic Marker and Mediator of Triple-Negative Breast Cancer Progression.
circEPSTI1 as a Prognostic Marker and Mediator of Triple-Negative Breast Cancer Progression.
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circEPSTI1 作为三阴性乳腺癌进展的预后标志物和调节因子
作者：
Chen B;Wei W;Huang X;Xie X;Kong Y;Dai D;Yang L;Wang J;Tang H;Xie X
环状RNA（circRNA）代表一类在调节基因表达和多种病理反应中起重要作用的非编码RNA。然而，circRNA在三阴性乳腺癌（TNBC）中的表达谱和功能仍然未知。在本研究中，我们研究了TNBC组织中人类circRNA的表达谱，并将circEPSTI 1（hsa_ circRNA_000479）鉴定为显著上调的circRNA。方法：我们进行了环状RNA微阵列分析，以筛选TNBC的环状RNA表达谱，并进一步研究circEPSTI 1。通过敲低circEPSTI 1基因，观察circEPSTI 1对TNBC细胞增殖、克隆形成和凋亡的影响。基于MRE分析和荧光素酶报告基因分析，我们发现circEPSTI 1作为miRNA海绵和miRNA的共靶基因与miRNA结合。我们在小鼠中进行了异种移植实验以证实我们的发现。我们通过ISH评估了240例TNBC患者的circEPSTI 1水平。结果：敲低circEPSTI 1可抑制TNBC细胞增殖并诱导其凋亡。体外和体内实验表明，circEPSTI 1作为miRNA海绵与miR-4753和miR-6809结合，调节BCL 11 A表达并影响TNBC增殖和凋亡。高水平的circEPSTI 1与TNBC患者的生存率降低相关。结论：circEPSTI 1-miR-4753/6809-BCL 11 A轴通过竞争内源性RNA（ceRNA）机制影响三阴性乳腺癌的增殖和凋亡。此外，我们的研究结果将circEPSTI 1确定为TNBC患者生存的独立预后标志物。
Circular RNAs (circRNAs) represent a class of non-coding RNAs that play a vital role in modulating gene expression and several pathological responses. However, the expression profile and function of circRNAs in triple-negative breast cancer (TNBC) remain unknown. In the current study, we investigated the expression profile of human circRNAs in TNBC tissues and identified circEPSTI1 (hsa_ circRNA_000479) as a significantly upregulated circRNA. Methods: We performed circular RNA microarray assays to screen circular RNA expression profiles of TNBC and further investigated circEPSTI1. We observed the effect of circEPSTI1 on proliferation, clonal formation and apoptosis in TNBC by knocking downcircEPSTI1 in three TNBC cell lines. Based on the MRE analysis and luciferase reporter assay, we found that circEPSTI1 binds to miRNAs as a miRNA sponge and the co-target genes of miRNAs. We performed xenograft experiments in mice to confirm our findings. We evaluated circEPSTI1 levels in 240 TNBC patients by ISH. Results: Knockdown of circEPSTI1 inhibits TNBC cell proliferation and induces apoptosis. In vitro and in vivo experiments indicated that circEPSTI1 binds to miR-4753 and miR-6809 as a miRNA sponge to regulate BCL11A expression and affect TNBC proliferation and apoptosis. High levels of circEPSTI1 correlate with reduced survival in TNBC patients. Conclusions: The circEPSTI1-miR-4753/6809-BCL11A axis affect the proliferation and apoptosis of triple-negative breast cancer through the mechanism of competing endogenous RNAs (ceRNA). In addition, our results identify circEPSTI1 as an independent prognostic marker for survival in patients with TNBC.
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影响因子：
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作者：
Nair AA;Niu N;Tang X;Thompson KJ;Wang L;Kocher JP;Subramanian S;Kalari KR
通讯作者：
Kalari KR
影响因子：
--
作者：
Li F;Zhang L;Li W;Deng J;Zheng J;An M;Lu J;Zhou Y
通讯作者：
Zhou Y
影响因子：
45.3
作者：
Heerema, NA;Sather, HN;Uckun, FM
通讯作者：
Uckun, FM
在小鼠慢性淋巴细胞性白血病中，染色体区域的丧失与人类13q14的同步13q14发生，该白血病源自早期生成的B-1 B细胞。
影响因子：
11.4
作者：
Hayakawa K;Formica AM;Colombo MJ;Shinton SA;Brill-Dashoff J;Morse Iii HC;Li YS;Hardy RR
通讯作者：
Hardy RR
DOI：
10.1261/rna.047126.114
发表时间：
2014-12
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Lasda E;Parker R
通讯作者：
Parker R