circ-NOL10 regulated by MTDH/CASC3 inhibits breast cancer progression and metastasis via multiple miRNAs and PDCD4.
circ-NOL10 regulated by MTDH/CASC3 inhibits breast cancer progression and metastasis via multiple miRNAs and PDCD4.
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DOI：
10.1016/j.omtn.2021.09.013
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发表时间：
2021-12-03
期刊：
影响因子：
--
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Cai Y;Zhao X;Chen D;Zhang F;Chen Q;Shao CC;Ouyang YX;Feng J;Cui L;Chen M;Xu J
环状RNA（circRNA）在肿瘤发生中起重要作用。在这里，我们研究了乳腺癌中高度抑制的circRNA circ-NOL 10的机制和临床意义。随后，我们还鉴定了调节circ-NOL 10的RNA结合蛋白（RBP）。利用生物信息学分析来预测调控RBP以及circ-NOL 10下游microRNA（miRNA）和mRNA靶标。RNA免疫沉淀、荧光素酶测定、荧光原位杂交、细胞增殖、伤口愈合、Matrigel侵袭、细胞凋亡测定和异种移植模型被用于研究circ-NOL 10在体外和体内的功能和机制。通过实时定量PCR在一个大型乳腺癌队列中评估circ-NOL 10的临床价值。Circ-NOL 10在乳腺癌中下调，并与侵袭性特征和较短的生存时间相关。circ-NOL 10的上调促进细胞凋亡，降低增殖，并抑制侵袭和迁移。此外，circ-NOL 10与多种miRNA结合，通过调节PDCD 4来缓解致癌作用。CASC 3和metadherin（MTDH）可以直接结合具有特征基序的circ-NOL 10。因此，CASC 3或MTDH的异位表达或缺失导致circ-NOL 10表达变化，表明这两种RBP调节癌细胞中的circ-NOL 10。circ-NOL 10是乳腺癌诊断和预后的新生物标志物。这些结果突出了治疗靶向RBP非编码RNA（ncRNA）调控网络的重要性。鉴定了由两种RBP（MTDH和CASC 3）、一种circRNA（circ-NOL 10）、三种miRNA（miR-149- 5 p、miR-330- 3 p和miR-452- 5 p）和效应物PDCD 4形成的新型RBP-ncRNA信号传导途径。这项研究揭示了ncRNA介导的乳腺癌发生机制，并为ncRNA的治疗靶向提供了新的见解。
Circular RNAs (circRNAs) play important roles in carcinogenesis. Here, we investigated the mechanisms and clinical significance of circ-NOL10, a highly repressed circRNA in breast cancer. Subsequently, we also identified RNA-binding proteins (RBPs) that regulate circ-NOL10. Bioinformatics analysis was utilized to predict regulatory RBPs as well as circ-NOL10 downstream microRNAs (miRNAs) and mRNA targets. RNA immunoprecipitation, luciferase assay, fluorescence in situ hybridization, cell proliferation, wound healing, Matrigel invasion, cell apoptosis assays, and a xenograft model were used to investigate the function and mechanisms of circ-NOL10 in vitro and in vivo. The clinical value of circ-NOL10 was evaluated in a large cohort of breast cancer by quantitative real-time PCR. Circ-NOL10 is downregulated in breast cancer and associated with aggressive characteristics and shorter survival time. Upregulation of circ-NOL10 promotes apoptosis, decreases proliferation, and inhibits invasion and migration. Furthermore, circ-NOL10 binds multiple miRNAs to alleviate carcinogenesis by regulating PDCD4. CASC3 and metadherin (MTDH) can bind directly to circ-NOL10 with characterized motifs. Accordingly, ectopic expression or depletion of CASC3 or MTDH leads to circ-NOL10 expression changes, suggesting that these two RBPs modulate circ-NOL10 in cancer cells. circ-NOL10 is a novel biomarker for diagnosis and prognosis in breast cancer. These results highlight the importance of therapeutic targeting of the RBP-noncoding RNA (ncRNA) regulation network. A novel RBP-ncRNA signaling route, formed by two RBPs (MTDH and CASC3), one circRNA (circ-NOL10), three miRNAs (miR-149-5p, miR-330-3p, and miR-452-5p), and the effector PDCD4, is identified. This investigation reveals a ncRNA-mediated mechanism in breast cancer carcinogenesis and provides novel insights for therapeutic targeting of ncRNAs.
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影响因子：
14.9
作者：
Cho S;Jang I;Jun Y;Yoon S;Ko M;Kwon Y;Choi I;Chang H;Ryu D;Lee B;Kim VN;Kim W;Lee S
通讯作者：
Lee S
DOI：
10.1186/s13046-019-1398-2
发表时间：
2019-09-05
影响因子：
11.3
作者：
Ren, Shasha;Liu, Jiuzhou;Zhang, Yanwu
通讯作者：
Zhang, Yanwu
影响因子：
11.2
作者：
Robertson CL;Mendoza RG;Jariwala N;Dozmorov M;Mukhopadhyay ND;Subler MA;Windle JJ;Lai Z;Fisher PB;Ghosh S;Sarkar D
通讯作者：
Sarkar D
DOI：
10.1186/bcr3343
发表时间：
2012-10-26
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Meric-Bernstam F;Chen H;Akcakanat A;Do KA;Lluch A;Hennessy BT;Hortobagyi GN;Mills GB;Gonzalez-Angulo A
通讯作者：
Gonzalez-Angulo A
影响因子：
4.1
作者：
Dudekulay, Dawood B.;Panda, Amaresh C.;Gorospe, Myriam
通讯作者：
Gorospe, Myriam