MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL.

MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL.
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MiR-92b-3p 通过靶向 circCDYL 抑制 HER2 阳性乳腺癌细胞的增殖

DOI:
10.3389/fcell.2021.707049
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发表时间:
2021
影响因子:
5.5
通讯作者:
Gong C
Gong C
中科院分区:
生物学2区
文献类型:
--
作者:
Liang G;Ling Y;Lin Q;Shi Y;Luo Q;Cen Y;Mehrpour M;Hamai A;Li J;Gong C

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目的环状RNA(circular RNA,circRNA)是一类新发现的RNA,在调节多种肿瘤细胞命运方面具有重要的生物学功能。之前,我们已经证明了circRNA circCDYL的过表达通过miR-1275-ULK 1/ATG 7-自噬轴促进HER 2阴性(HER 2-)乳腺癌的进展。然而,circCDYL在HER 2阳性(HER 2+)乳腺癌中的作用,特别是其在调节细胞增殖(细胞命运的最重要特征之一)中的作用尚不清楚。材料与方法采用qRT-PCR和原位杂交技术检测乳腺癌组织或细胞系中circCDYL和miR-92 b-3 p的表达。通过平板集落形成和细胞活力测定以及原位动物模型评估circCDYL和miR-92 b-3 p的生物学功能。在机制研究中,进行了circRNAs pull-down、RNA免疫沉淀、双荧光素酶报告、western blot、免疫组织化学和免疫荧光染色测定。结果CircCDYL在HER 2+乳腺癌组织中呈高表达,与HER 2-乳腺癌组织相似。沉默HER 2基因对HER 2+乳腺癌细胞中circCDYL的表达没有影响。circCDYL的过表达促进HER 2+乳腺癌细胞的增殖,但不是通过miR-1275-ULK 1/ATG 7-自噬轴。CircRNA pull down和miRNA深度测序证实了miR-92 b-3 p和circCDYL的结合。有趣的是,circCDYL不充当miR-92 b-3 p海绵,而是以miR-92 b-3 p依赖性沉默方式降解。临床上,circCDYL和miR-92 b-3 p的表达与HER 2+乳腺癌患者的临床结局相关。结论miR-92 b-3 p依赖的cyclCDYL切割是HER 2+乳腺癌细胞增殖调控的重要机制。CircCDYL被证明是HER 2+乳腺癌的潜在治疗靶点,circCDYL和miR-92 b-3 p可能是预测HER 2+乳腺癌患者临床结局的潜在生物标志物。
Objectives Circular RNA (circRNA) is a novel class of RNA, which exhibits powerful biological function in regulating cellular fate of various tumors. Previously, we had demonstrated that over-expression of circRNA circCDYL promoted progression of HER2-negative (HER2–) breast cancer via miR-1275-ULK1/ATG7-autophagic axis. However, the role of circCDYL in HER2-positive (HER2+) breast cancer, in particular its role in modulating cell proliferation, one of the most important characteristics of cellular fate, is unclear. Materials and methods qRT-PCR and in situ hybridization analyses were performed to examine the expression of circCDYL and miR-92b-3p in breast cancer tissues or cell lines. The biological function of circCDYL and miR-92b-3p were assessed by plate colony formation and cell viability assays and orthotopic animal models. In mechanistic study, circRNAs pull-down, RNA immunoprecipitation, dual luciferase report, western blot, immunohistochemical and immunofluorescence staining assays were performed. Results CircCDYL was high-expressed in HER2+ breast cancer tissue, similar with that in HER2– breast cancer tissue. Silencing HER2 gene had no effect on expression of circCDYL in HER2+ breast cancer cells. Over-expression of circCDYL promoted proliferation of HER2+ breast cancer cells but not through miR-1275-ULK1/ATG7-autophagic axis. CircRNA pull down and miRNA deep-sequencing demonstrated the binding of miR-92b-3p and circCDYL. Interestingly, circCDYL did not act as miR-92b-3p sponge, but was degraded in miR-92b-3p-dependent silencing manner. Clinically, expression of circCDYL and miR-92b-3p was associated with clinical outcome of HER2+ breast cancer patients. Conclusion MiR-92b-3p-dependent cleavage of circCDYL was an essential mechanism in regulating cell proliferation of HER2+ breast cancer cells. CircCDYL was proved to be a potential therapeutic target for HER2+ breast cancer, and both circCDYL and miR-92b-3p might be potential biomarkers in predicting clinical outcome of HER2+ breast cancer patients.
DOI: 10.1371/journal.pgen.1009058
发表时间: 2020-11
期刊: PLoS genetics
影响因子: 4.5
作者:
Marzec M
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DOI: 10.1093/jnci/djx166
发表时间: 2018-03-01
期刊: Journal of the National Cancer Institute
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作者:
Yang Y;Gao X;Zhang M;Yan S;Sun C;Xiao F;Huang N;Yang X;Zhao K;Zhou H;Huang S;Xie B;Zhang N
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DOI: 10.1186/s12938-021-00857-9
发表时间: 2021-02-16
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DOI: 10.3892/ol.2020.12265
发表时间: 2021-01
期刊: Oncology letters
影响因子: 2.9
作者:
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自噬相关的 circRNA circCDYL 增强自噬并促进乳腺癌进展
DOI: 10.1186/s12943-020-01152-2
发表时间: 2020-03-25
期刊: MOLECULAR CANCER
影响因子: 37.3
作者:
Liang, Gehao;Ling, Yun;Gong, Chang
通讯作者: Gong, Chang