hsa_circ_0000231 Promotes colorectal cancer cell growth through upregulation of CCND2 by IGF2BP3/miR-375 dual pathway.

hsa_circ_0000231 Promotes colorectal cancer cell growth through upregulation of CCND2 by IGF2BP3/miR-375 dual pathway.
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hsa_circ_0000231 通过 IGF2BP3/miR-375 双通路上调 CCND2 促进结直肠癌细胞生长

DOI:
10.1186/s12935-022-02455-8
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发表时间:
2022-01-15
影响因子:
5.8
通讯作者:
Shen Z
Shen Z
中科院分区:
医学2区
文献类型:
--
作者:
Zhang W;Wang B;Lin Y;Yang Y;Zhang Z;Wang Q;Zhang H;Jiang K;Ye Y;Wang S;Shen Z

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环状RNA(circRNA)已成为多种人类癌症发生和发展的重要调节因子。本研究探讨hsa_circ_0000231及其下游通路在结直肠癌中的作用。采用基因芯片技术分析5对大肠癌组织及癌旁正常组织中circRNA的表达谱。使用定量实时PCR和原位杂交以及Base Scope Assay来确定hsa_circ_0000231的水平和预后价值。然后,进行体外和体内功能实验以研究hsa_circ_0000231对细胞增殖的影响。在机制上,进行荧光原位杂交、双荧光素酶报告基因测定、RNA下拉和RNA免疫沉淀实验,以证实hsa_circ_0000231与IGF 2BP 3或has_miR-375之间的相互作用。我们通过circRNA微阵列获得的数据显示,与癌旁正常组织相比,hsa_circ_0000231在CRC原发组织中的表达上调,这表明CRC患者预后不良。功能分析表明,在CRC细胞系中抑制hsa_circ_0000231可以抑制CRC细胞增殖以及体内外的肿瘤发生。机制分析表明,hsa_circ_0000231可能一方面作为miR-375的竞争性内源性RNA来促进细胞周期蛋白D2(CCND 2),另一方面与IGF 2BP 3蛋白结合来阻止CCND 2降解。研究结果表明,hsa_circ_0000231通过海绵状的miR-375或结合IGF 2BP 3调节CCND 2促进CRC进展,这意味着hsa_circ_0000231可能是一个潜在的新的CRC诊断和治疗生物标志物。在线版本包含补充材料,可通过10.1186/s12935-022-02455-8获得。
Circular RNAs (circRNAs) have emerged as vital regulators of the initiation and progression of diverse kinds of human cancers. In this study, we explored the role of hsa_circ_0000231 and its downstream pathway in CRC. The expression profile of circRNAs in 5 pairs of CRC tissues and adjacent normal tissues were analyzed by Microarray. Quantitative real-time PCR and in situ hybridization and Base Scope Assay were used to determine the level and prognostic values of hsa_circ_0000231. Then, functional experiments in vitro and in vivo were performed to investigate the effects of hsa_circ_0000231 on cell proliferation. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between hsa_circ_0000231 and IGF2BP3 or has_miR-375. We acquired data through circRNA microarray profiles, showing that the expression of hsa_circ_0000231 was upregulated in CRC primary tissues compared to adjacent normal tissues, which was indicated poor prognosis of patients with CRC. Functional analysis indicated that inhibition of hsa_circ_0000231 in CRC cell lines could suppress CRC cell proliferation as well as tumorigenesis in vitro and in vivo. The mechanistic analysis showed that hsa_circ_0000231 might, on the one hand, act as a competing endogenous RNA of miR-375 to promote cyclin D2 (CCND2) and, on the other hand, bind to the IGF2BP3 protein to prevent CCND2 degradation. The findings suggested that hsa_circ_0000231 facilitated CRC progression by sponging miR-375 or binding to IGF2BP3 to modulate CCND2, implying that hsa_circ_0000231 might be a potential new diagnostic and therapeutic biomarker of CRC. The online version contains supplementary material available at 10.1186/s12935-022-02455-8.
DOI: 10.1186/s13046-021-02074-7
发表时间: 2021-08-27
期刊: Journal of experimental & clinical cancer research : CR
影响因子: --
作者:
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DOI: 10.1007/978-981-13-1426-1_6
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期刊: CIRCULAR RNAS: BIOGENESIS AND FUNCTIONS
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环状 RNA 分析将 circADAMTS13 鉴定为 miR-484 海绵,可抑制肝细胞癌中的细胞增殖
DOI: 10.1002/1878-0261.12424
发表时间: 2019-02-01
期刊: MOLECULAR ONCOLOGY
影响因子: 6.6
作者:
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