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

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.

Highly expressed ribosomal protein L34 predicts poor prognosis in acute myeloid leukemia and could be a potential therapy target

“…In order to define the role of RPL34 in AML, we constructed shRPL34-lentivirus to successfully knockdown RPL34 in HL-60 cell line, a commonly used AML cell line. Consistent with other studies performed in solid tumors [8][9], we found knockdown of RPL34 could significantly inhibit cell proliferation and trigger apoptosis. In cell cycle distribution analysis, more HL-60 cells transfected with shRPL34 lentivirus were arrested in S phase.…”

“…Ribosomal proteins (RPs) play important roles in cell proliferation and growth in most eukaryotic cells [7]. However, in recent years, increasing evidence has shown RPs may involve in the process of tumorigenesis, metastasis, and therapy resistance [7,[9][10][11] have been reported to reveal the role of RPL34, one type of ribosomal protein, in solid tumors [8][9]. To the best of our knowledge, the present study is the first to investigate the expression and clinical significance of RPL34 in AML.…”

“…Indeed, patients who got complete response after induction therapy and enjoyed long-term survival had significantly lower level of RPL34 than those that failed induction therapies and suffered from recurrent disease relapses ( Figure 1C). Previous studies have reported that RPL34 promotes tumorigenesis through affecting cell proliferation, apoptosis, and cell cycle distribution [7][8][9]. In order to define the role of RPL34 in AML, we constructed shRPL34-lentivirus to successfully knockdown RPL34 in HL-60 cell line, a commonly used AML cell line.…”

Exploring the key genes and pathways of side population cells in human osteosarcoma using gene expression array analysis

“…Ajiro et al found that serine/arginine-rich splicing factor 3 (SRSF3) regulates the expression of DDX5 in human OS U2OS cells [ 30 ]. By participating in the transcriptional regulation of ribosomal protein L34 (RPL34) which plays an important role in the proliferation of OS cells, MYC interacts with the subunits of EIF3 and probably involves the translational control of growth-promoting proteins [ 31 ]. EIF3, a multi-subunit complex, plays a critical role in translation initiation.…”

The nucleolus, an ally, and an enemy of cancer cells

“…Likewise, RPL34 overexpression in osteosarcoma promotes proliferation of malignant cells. In this case, RPL34, whose transcription is regulated by c-Myc, cooperates with certain subunits of the important initiating translation factor (eIF3) which probably results in increased protein biosynthesis, including those promoting growth (Luo et al 2016 ). In the pancreatic cancer (PC) cells, RPL34 is hyperexpressed most probably through hypomethylation of the promoter of a gene encoding this protein.…”