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Hsa_circ_0002005通过增加细胞增殖、迁移和侵袭来加重骨肉瘤。

Hsa_circ_0002005 aggravates osteosarcoma by increasing cell proliferation, migration, and invasion.

作者信息

Yang Junxu, Hu Zizhu, Ru Xiao, He Mingwei, Hu Ziwei, Qin Xiong, Xiao Shihui, Liu Dachang, Huang Hanji, Wei Qingjun

机构信息

Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi, PR China; Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi, PR China.

Southern Medical University, 510000 Guangzhou, PR China.

出版信息

Gene. 2025 Mar 20;942:149221. doi: 10.1016/j.gene.2025.149221. Epub 2025 Jan 4.

Abstract

Emerging evidence suggests that circular RNAs (circRNAs), a class of non-coding RNAs, play a critical role in the progression of several cancers, including osteosarcoma (OS). In this study, we focused on a specific circRNA, hsa_circ_0002005, derived from the mesoderm-induced early response 1 family member 2 (MIER2) gene. We determined the expression levels of hsa_circ_0002005 in OS samples through the use of real-time quantitative polymerase chain reaction (RT-qPCR). To assess the effect of hsa_circ_0002005, we used lentiviral analysis and performed several assays including transwell migration, cell invasion, 5-ethynyl-2'-deoxyuridine assay (EdU), cell counting kit-8 (CCK-8), proliferation, colony formation, and western blotting. In addition, we investigated the delivery mechanism of hsa_circ_0002005 in nude mice and predicted the interaction network involving hsa_circ_0002005, microRNA (miRNA), and mRNAs through bioinformatics analysis. The results showed that hsa_circ_0002005 is overexpressed in OS tissues and cells and is derived from exons 2 to 7 of the MIER2 gene. Knockdown of hsa_circ_0002005 markedly reduced the proliferation, migration, and invasive capabilities of cells, as well as their metastatic potential. We discovered miRNAs that may engage with hsa_circ_0002005. Further mechanistic studies indicated that the suppression of hsa_circ_0002005 influenced the expression levels of proteins associated with the epithelial-mesenchymal transition (EMT), suggesting its regulatory role in EMT progression through modulation of cell proliferation, migration, and invasion.

摘要

新出现的证据表明,环状RNA(circRNA)作为一类非编码RNA,在包括骨肉瘤(OS)在内的多种癌症进展中发挥关键作用。在本研究中,我们聚焦于一种特定的circRNA,即源自中胚层诱导早期反应1家族成员2(MIER2)基因的hsa_circ_0002005。我们通过实时定量聚合酶链反应(RT-qPCR)测定了hsa_circ_0002005在OS样本中的表达水平。为评估hsa_circ_0002005的作用,我们采用慢病毒分析并进行了多项实验,包括Transwell迁移实验、细胞侵袭实验、5-乙炔基-2'-脱氧尿苷检测(EdU)、细胞计数试剂盒-8(CCK-8)实验、增殖实验、集落形成实验以及蛋白质免疫印迹法。此外,我们研究了hsa_circ_0002005在裸鼠中的递送机制,并通过生物信息学分析预测了涉及hsa_circ_0002005、微小RNA(miRNA)和信使核糖核酸(mRNA)的相互作用网络。结果显示,hsa_circ_0002005在OS组织和细胞中过表达,且源自MIER2基因的外显子2至7。敲低hsa_circ_0002005可显著降低细胞的增殖、迁移和侵袭能力及其转移潜能。我们发现了可能与hsa_circ_0002005相互作用的miRNA。进一步的机制研究表明,抑制hsa_circ_0002005会影响与上皮-间质转化(EMT)相关蛋白质的表达水平,提示其通过调节细胞增殖、迁移和侵袭在上皮-间质转化进程中发挥调控作用。

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