Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR-653-5p.
Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR-653-5p.
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Hsa_circ_0003258 通过与 IGF2BP3 复合并海绵 miR-653-5p 促进前列腺癌转移
DOI：
10.1186/s12943-021-01480-x
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发表时间：
2022-01-05
期刊：
影响因子：
37.3
通讯作者：
Zhao SC
中科院分区：
文献类型：
--
作者：
Yu YZ;Lv DJ;Wang C;Song XL;Xie T;Wang T;Li ZM;Guo JD;Fu DJ;Li KJ;Wu DL;Chan FL;Feng NH;Chen ZS;Zhao SC
越来越多的研究表明，环状RNA（circRNA）在许多癌症中起着重要的调控作用。然而，circRNA在前列腺癌（PCa）中的潜在分子机制在很大程度上仍然未知。通过RNA测序鉴定差异表达的circRNA。使用定量实时PCR和RNA原位杂交评估hsa_circ_0003258的表达。通过一系列体外和体内试验研究hsa_circ_0003258对PCa细胞转移的影响。最后，通过Western blot、生物素标记的RNA pulldown、RNA免疫沉淀、荧光素酶测定和拯救实验揭示了hsa_circ_0003258的潜在机制。hsa_circ_0003258在PCa组织中的表达增加，并且与晚期TNM分期和ISUP分级相关。hsa_circ_0003258的过表达通过诱导体外上皮间质转化（EMT）以及体内肿瘤转移促进PCa细胞迁移，而hsa_circ_0003258的敲低发挥相反的作用。从机制上讲，hsa_circ_0003258可以通过海绵状miR-653- 5 p来提高Rho GTPase激活蛋白5（ARHGAP 5）的表达。此外，hsa_circ_0003258与细胞质中的胰岛素样生长因子2 mRNA结合蛋白3（IGF 2BP 3）物理结合并增强HDAC 4 mRNA稳定性，其中其激活ERK信号通路，然后触发EMT编程并最终加速PCa的转移。hsa_circ_0003258的上调通过hsa_circ_0003258/miR-653- 5 p/ARHGAP 5轴和hsa_circ_0003258/IGF 2BP 3/HDAC 4轴驱动肿瘤进展。Hsa_circ_0003258可能作为PCa转移的有希望的生物标志物和PCa干预的有吸引力的靶点。在线版本包含补充材料，可通过10.1186/s12943-021-01480-x获得。
More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo, while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention. The online version contains supplementary material available at 10.1186/s12943-021-01480-x.
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DOI：
10.1016/j.bbrc.2019.03.214
发表时间：
2019-06-11
影响因子：
3.1
作者：
Guo, Jianbo;Duan, He;Yuan, Lu
通讯作者：
Yuan, Lu
影响因子：
3.3
作者：
Li, Yuhui;Zang, Hongliang;Huang, Guomin
通讯作者：
Huang, Guomin
影响因子：
3
作者：
Jiang, H.;Lv, D. J.;Zhao, S. C.
通讯作者：
Zhao, S. C.
影响因子：
4.7
作者：
Noronha C;Ribeiro AS;Taipa R;Castro DS;Reis J;Faria C;Paredes J
通讯作者：
Paredes J
HDAC4 促进鼻咽癌进展并作为治疗靶点。
影响因子：
9
作者：
Cheng C;Yang J;Li SW;Huang G;Li C;Min WP;Sang Y
通讯作者：
Sang Y