piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer.
piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer.
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DOI：
10.3389/fcell.2021.641052
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发表时间：
2021
影响因子：
5.5
通讯作者：
Yu Z
中科院分区：
文献类型：
--
作者：
Ding X;Li Y;Lü J;Zhao Q;Guo Y;Lu Z;Ma W;Liu P;Pestell RG;Liang C;Yu Z
癌症干细胞（CSCs）被认为是癌症复发和转移的主要来源。PIWI相互作用的小非编码RNA（piRNA）最近被认为与癌症生物学相关。piRNA是否以及如何调节人类CSC仍然未知。在本文中，在测试的管腔型乳腺癌细胞中，特别是在乳腺CSC的管腔亚型中鉴定了piR-823的上调。piR-823的增强表达或靶向敲低证实了其在MCF-7和T-47 D乳腺癌细胞中调节细胞增殖和集落形成的致癌功能。此外，piR-823诱导的ALDH（+）乳腺CSC亚群促进干细胞标志物（包括OCT 4、SOX 2、KLF 4、NANOG和hTERT）的表达，并增加乳腺球形成。将携带抗piR-823的磁性纳米颗粒尾静脉注射到荷瘤小鼠的乳腺中可显着抑制体内肿瘤生长。DNA甲基转移酶（DNMTs）包括DNMT 1、DNMT 3A和DNMT 3B被证明是piR-823的下游基因，其通过维持DNA甲基化来调节基因表达。piR-823增加DNMT的表达，促进基因腺瘤性结肠息肉病（APC）的DNA甲基化，从而激活Wnt信号传导并诱导管腔亚型乳腺癌细胞中的癌细胞干性。目前的研究不仅揭示了piRNA通过调节CSC促进乳腺癌肿瘤发生的新机制，而且还提供了使用非编码基因组抑制人类乳腺癌的治疗策略。
Cancer stem cells (CSCs) are believed to be the main source of cancer relapse and metastasis. PIWI-interacting small non-coding RNAs (piRNAs) have been recently recognized to be relevant to cancer biology. Whether and how piRNAs regulate human CSCs remain unknown. Herein, upregulation of piR-823 was identified in tested luminal breast cancer cells, especially in the luminal subtype of breast CSCs. Enforced expression or targeted knockdown of piR-823 demonstrated its oncogenic function in regulating cell proliferation and colony formation in MCF-7 and T-47D breast cancer cells. In addition, piR-823 induced ALDH (+) breast CSC subpopulation promoted the expression of stem cell markers including OCT4, SOX2, KLF4, NANOG, and hTERT, and increased mammosphere formation. Tail vein injection of magnetic nanoparticles carrying anti-piR-823 into the mammary gland of tumor-burdened mice significantly inhibited tumor growth in vivo. DNA methyltransferases (DNMTs) including DNMT1, DNMT3A, and DNMT3B were demonstrated to be the downstream genes of piR-823, which regulate gene expression by maintaining DNA methylation. piR-823 increased the expression of DNMTs, promoted DNA methylation of gene adenomatous polyposis coli (APC), thereby activating Wnt signaling and inducing cancer cell stemness in the luminal subtype of breast cancer cells. The current study not only revealed a novel mechanism through which piRNAs contribute to tumorigenesis in breast cancer by regulating CSCs, but also provided a therapeutic strategy using non-coding genomes in the suppression of human breast cancer.
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DOI：
10.1038/nrc.2017.99
发表时间：
2018-01
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Anastasiadou E;Jacob LS;Slack FJ
通讯作者：
Slack FJ
影响因子：
--
作者：
Amaar YG;Reeves ME
通讯作者：
Reeves ME
Cyclin D1 介导的 microRNA 表达特征控制乳腺癌结果
影响因子：
12.4
作者：
Wang G;Gormley M;Qiao J;Zhao Q;Wang M;Di Sante G;Deng S;Dong L;Pestell T;Ju X;Casimiro MC;Addya S;Ertel A;Tozeren A;Li Q;Yu Z;Pestell RG
通讯作者：
Pestell RG
影响因子：
37.3
作者：
Ai, Lisha;Mu, Shidai;Hu, Yu
通讯作者：
Hu, Yu
影响因子：
3.6
作者：
Arnold, CN;Goel, A;Boland, CR
通讯作者：
Boland, CR