Dissecting the role of the elongation factor 1A isoforms in hepatocellular carcinoma cells by liposome-mediated delivery of siRNAs

Farra, Rossella; Scaggiante, Bruna; Guerra, Chiara; Pozzato, Gabriele; Grassi, Mario; Zanconati, Fabrizio; Perrone, Francesca; Ferrari, Cinzia; Trotta, Francesco; Dapas, Barbara

doi:10.1016/j.ijpharm.2017.02.031

Cited by 18 publications

(18 citation statements)

References 39 publications

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“…Indeed, a detailed knowledge of nanostructure is mandatory to properly design and optimize drug delivery system based on polymers such as IPN. This is particularly true in the case of the release of active agents that need to be embedded inside liposomes or on their surface in order to protect them till they reach the site action as it happens in the case of the fragile Nucleic Acid Based Drugs [31][32][33][34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Combined Used of Rheology and LF-NMR for the Characterization of PVP-Alginates Gels Containing Liposomes

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Combined Used of Rheology and LF-NMR for the Characterization of PVP-Alginates Gels Containing Liposomes

et al. 2018

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“…Among these processes, the eukaryotic elongation factor 1 (eEF1) complex plays an indispensable function in eukaryotic protein peptide chain elongation in all eukaryotic cells [13] , [14] . eEF1A1, eukaryotic elongation factor 1 alpha 1 (eEF1A2) and eEF1Bαβγ subcomplex [15] . Human eEF1A1 is a core subunit of the eEF1 complex that shows ability for GTP binding as well as amino acid-tRNA delivery [16] .…”

Section: Introductionmentioning

confidence: 99%

“…Blanch et al [24] suggested that eEF1A1 was a negative regulator of p53 and p73, since silencing of eEF1A1 partially rescued the anti-apoptosis and chemoresistance observed in response to p53 or p73 knockdown. Farra et al [15] reported that eEF1A1 depletion in HCC downregulated the transcription factor E2F1 to induce the G1/G0 cell cycle block. However, the clinical significance of eEF1A1 in tumor development and progression has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

eEF1A1 Overexpression Enhances Tumor Progression and Indicates Poor Prognosis in Hepatocellular Carcinoma

Chen

Liu

et al. 2018

Translational Oncology

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Liver is a major contributor of protein production physiologically. The aberrant state of protein synthesis leads to tumor progression. Eukaryotic elongation factor 1 alpha 1 (eEF1A1) is a major member of the eukaryotic elongation factor family that regulates protein synthesis. Although eEF1A1 plays an essential role in controlling the cell fate, its clinical significance in tumor development and progression has not been reported. Here, we aimed to uncover the expression and prognostic significance of eEF1A1 in hepatocellular carcinoma (HCC). Our data indicated that eEF1A1 expression was elevated in HCC cell lines and clinical samples at both the mRNA and protein levels. Immunohistochemistry revealed that eEF1A1 expression was upregulated in HCC samples compared with corresponding non-tumorous tissues. In 50 HCC cases with portal vein embolus, higher eEF1A1 immunoreactivity was detected in tumor metastases compared with the primary lesions. Kaplan–Meier analysis indicated that increased eEF1A1 expression was closely associated with unfavorable post-surgical overall and disease-free survival in 453 HCC patients. Moreover, multivariate analysis indicated eEF1A1 as an independent predictor for overall and disease-free survival. Collectively, our study suggests eEF1A1 as a novel prognostic biomarker and potential therapeutic target for HCC patients.

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“…LMNA (A-type lamin) has been shown to control transcription of BRCA1 [47]. EEF1A1 (translation elongation factor 1-alpha 1) affects gene expression through regulating mRNA stability [48], and could also regulate BRCA1 through E2F1 [50, 51]. Therefore, the ultimate BRCA1 protein level is regulated by CTSO at both transcription as well as protein levels.…”

Section: Discussionmentioning

confidence: 99%

SNPs near the cysteine proteinase cathepsin O gene (CTSO) determine tamoxifen sensitivity in ERα-positive breast cancer through regulation of BRCA1

et al. 2017

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Tamoxifen is one of the most commonly employed endocrine therapies for patients with estrogen receptor α (ERα)-positive breast cancer. Unfortunately the clinical benefit is limited due to intrinsic and acquired drug resistance. We previously reported a genome-wide association study that identified common SNPs near the CTSO gene and in ZNF423 associated with development of breast cancer during tamoxifen therapy in the NSABP P-1 and P-2 breast cancer prevention trials. Here, we have investigated their roles in ERα-positive breast cancer growth and tamoxifen response, focusing on the mechanism of CTSO. We performed in vitro studies including luciferase assays, cell proliferation, and mass spectrometry-based assays using ERα-positive breast cancer cells and a panel of genomic data-rich lymphoblastoid cell lines. We report that CTSO reduces the protein levels of BRCA1 and ZNF423 through cysteine proteinase-mediated degradation. We also have identified a series of transcription factors of BRCA1 that are regulated by CTSO at the protein level. Importantly, the variant CTSO SNP genotypes are associated with increased CTSO and decreased BRCA1 protein levels that confer resistance to tamoxifen. Characterization of the effect of both CTSO SNPs and ZNF423 SNPs on tamoxifen response revealed that cells with different combinations of CTSO and ZNF423 genotypes respond differently to Tamoxifen, PARP inhibitors or the combination of the two drugs due to SNP dependent differential regulation of BRCA1 levels. Therefore, these genotypes might be biomarkers for selection of individual drug to achieve the best efficacy.

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Dissecting the role of the elongation factor 1A isoforms in hepatocellular carcinoma cells by liposome-mediated delivery of siRNAs

Cited by 18 publications

References 39 publications

Combined Used of Rheology and LF-NMR for the Characterization of PVP-Alginates Gels Containing Liposomes

Combined Used of Rheology and LF-NMR for the Characterization of PVP-Alginates Gels Containing Liposomes

eEF1A1 Overexpression Enhances Tumor Progression and Indicates Poor Prognosis in Hepatocellular Carcinoma

SNPs near the cysteine proteinase cathepsin O gene (CTSO) determine tamoxifen sensitivity in ERα-positive breast cancer through regulation of BRCA1

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