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核糖体蛋白 L34 高表达预示着骨肉瘤预后不良,其敲低可能通过翻译调控抑制骨肉瘤增殖。

Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control.

机构信息

Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, China.

Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, Guangxi, 530021, China.

出版信息

Sci Rep. 2016 Nov 24;6:37690. doi: 10.1038/srep37690.

Abstract

Osteosarcoma has devastating health implications on children and adolescents. However, due to its low incidence and high tumor heterogeneity, it is hard to achieve any further improvements in therapy and overall survival. Ribosomal protein L34 (RPL34) has been increasingly recognized to promote the proliferation of malignant cells, but its role in osteosarcoma has not been investigated. In this study, real-time quantitative PCR (RT-qPCR) and immunohistochemistry revealed that RPL34 was highly expressed in osteosarcoma tissues when compared to adjacent tissues and normal bone tissues. Survival analysis showed that high expression of RPL34 predicted a poor prognosis for osteosarcoma patients. Knockdown of RPL34 in Saos-2 cells via lentivirus-mediated small interfering RNA (siRNA) significantly inhibited cell proliferation, induced cell apoptosis and G2/M phase arrest. Moreover, screening of transcription factors using University of California Santa Cruz (UCSC) Genome Browser, protein-protein interaction (PPI) network analysis, Gene Ontology (GO) and pathway enrichment analysis revealed that MYC participates in the transcriptional regulation of RPL34, which interacts with the subunits of eukaryotic translation initiation factor 3 (eIF3) and probably involves the translational control of growth-promoting proteins. Our findings suggest that RPL34 plays an important role in the proliferation of osteosarcoma cells.

摘要

骨肉瘤对儿童和青少年的健康有严重影响。然而,由于其发病率低和肿瘤异质性高,很难在治疗和总体生存率方面取得进一步的提高。核糖体蛋白 L34(RPL34)已被越来越多地认为可促进恶性细胞的增殖,但它在骨肉瘤中的作用尚未得到研究。在这项研究中,实时定量 PCR(RT-qPCR)和免疫组织化学显示,与相邻组织和正常骨组织相比,RPL34 在骨肉瘤组织中高度表达。生存分析表明,RPL34 的高表达预示着骨肉瘤患者预后不良。通过慢病毒介导的小干扰 RNA(siRNA)在 Saos-2 细胞中敲低 RPL34 显著抑制细胞增殖,诱导细胞凋亡和 G2/M 期阻滞。此外,使用加利福尼亚大学圣克鲁斯分校(UCSC)基因组浏览器筛选转录因子、蛋白质-蛋白质相互作用(PPI)网络分析、基因本体论(GO)和途径富集分析表明,MYC 参与 RPL34 的转录调控,与真核翻译起始因子 3(eIF3)的亚基相互作用,可能涉及生长促进蛋白的翻译控制。我们的研究结果表明,RPL34 在骨肉瘤细胞的增殖中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a512/5121591/70383dfff8ed/srep37690-f1.jpg

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