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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Integrated network and enrichment analysis.(A) Integrated network of TF-target and PPI. The TFs implicated in the transcriptional regulation of RPL34 and the proteins interacted with RPL34 are presented in green nodes and pink nodes, respectively. (B) GO analysis of the genes identified in PPI network. The enrichment of the genes associated with RPL34 in molecular function, cellular component and biological process revealed that RPL34 mainly involves in translational control, apart from ribosome biogenesis, probably through the interactions with the subunits of eIF3.
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f8: Integrated network and enrichment analysis.(A) Integrated network of TF-target and PPI. The TFs implicated in the transcriptional regulation of RPL34 and the proteins interacted with RPL34 are presented in green nodes and pink nodes, respectively. (B) GO analysis of the genes identified in PPI network. The enrichment of the genes associated with RPL34 in molecular function, cellular component and biological process revealed that RPL34 mainly involves in translational control, apart from ribosome biogenesis, probably through the interactions with the subunits of eIF3.

Mentions: The transcription factors (TFs) implicated in the transcriptional regulation of RPL34 were predicted based on UCSC database. The results indicated that eleven identified TFs, particularly MYC and MYC associated factor X (MAX), were involved in the transcriptional regulation of RPL34 (Fig. 8A). The MYC oncoprotein and MAX are frequently involved in cell proliferation, differentiation and apoptosis in the form of dimers. The PPI network constructed based on the information from STRING database composes of 112 nodes and 4669 interactions (Fig. 8A and Supplementary Table S1). GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the genes in PPI network were significantly enriched in a pathway known as ribosome and GO terms of different categories, namely molecular function (MF), cellular component (CC) and biological process (BP). The top 7 (or top 15) enriched GO terms of each category were listed in Table 1. The data indicated that the genes associated with RPL34 were mainly enriched in the GO terms related to structural constituent of ribosome and synthetic process of protein (Fig. 8B). Interestingly, each GO category, as MF termed translation factor activity and nucleic acid binding, CC termed eukaryotic translation initiation factor 3 complex and BP termed translational initiation, was significantly enriched by three identified genes in the PPI network, including EIF3A, EIF3G and EIF3F. The proteins encoded by these three genes are different subunits of the 13-subunit complex, namely eIF3. More importantly, specific individual subunits of eIF3 have been shown to be dysregulated in a wide range of human tumors.


Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control
Integrated network and enrichment analysis.(A) Integrated network of TF-target and PPI. The TFs implicated in the transcriptional regulation of RPL34 and the proteins interacted with RPL34 are presented in green nodes and pink nodes, respectively. (B) GO analysis of the genes identified in PPI network. The enrichment of the genes associated with RPL34 in molecular function, cellular component and biological process revealed that RPL34 mainly involves in translational control, apart from ribosome biogenesis, probably through the interactions with the subunits of eIF3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121591&req=5

f8: Integrated network and enrichment analysis.(A) Integrated network of TF-target and PPI. The TFs implicated in the transcriptional regulation of RPL34 and the proteins interacted with RPL34 are presented in green nodes and pink nodes, respectively. (B) GO analysis of the genes identified in PPI network. The enrichment of the genes associated with RPL34 in molecular function, cellular component and biological process revealed that RPL34 mainly involves in translational control, apart from ribosome biogenesis, probably through the interactions with the subunits of eIF3.
Mentions: The transcription factors (TFs) implicated in the transcriptional regulation of RPL34 were predicted based on UCSC database. The results indicated that eleven identified TFs, particularly MYC and MYC associated factor X (MAX), were involved in the transcriptional regulation of RPL34 (Fig. 8A). The MYC oncoprotein and MAX are frequently involved in cell proliferation, differentiation and apoptosis in the form of dimers. The PPI network constructed based on the information from STRING database composes of 112 nodes and 4669 interactions (Fig. 8A and Supplementary Table S1). GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the genes in PPI network were significantly enriched in a pathway known as ribosome and GO terms of different categories, namely molecular function (MF), cellular component (CC) and biological process (BP). The top 7 (or top 15) enriched GO terms of each category were listed in Table 1. The data indicated that the genes associated with RPL34 were mainly enriched in the GO terms related to structural constituent of ribosome and synthetic process of protein (Fig. 8B). Interestingly, each GO category, as MF termed translation factor activity and nucleic acid binding, CC termed eukaryotic translation initiation factor 3 complex and BP termed translational initiation, was significantly enriched by three identified genes in the PPI network, including EIF3A, EIF3G and EIF3F. The proteins encoded by these three genes are different subunits of the 13-subunit complex, namely eIF3. More importantly, specific individual subunits of eIF3 have been shown to be dysregulated in a wide range of human tumors.

View Article: PubMed Central - PubMed

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.

No MeSH data available.