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The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. However, the role of eukaryotic translation initiation factor 3 subunit D (EIF3D) in cervical carcinoma is unknown. This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. There were increases of EIF3D expression mRNA and protein expression levels in patients with cervical carcinoma. Disease-free survival (DFS) and overall surviva (OS) of EIF3D lower expression in patients with cervical carcinoma was higher than those of EIF3D higher expression. EIF3D mRNA expression levels in cervical carcinoma cell lines (AV3, Hela229, CaSki and Hela cells) were up-regulated, compared with cervical normal cell line (UVECs). EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma. EIF3D interacting with GRP78 to reduce the activity of GRP78 in vitro model of cervical carcinoma. The inhibition of GRP78 reduced the effects of EIF3D on Warburg effect in vitro model of cervical carcinoma. Our work identifies EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma.IMPACT STATEMENT What is already known on this subject? The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. What do the results of this study add? This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. What are the implications of these findings for clinical practice and/or further research? EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma.

Autoimmune destruction of pancreatic beta cells causes absolute insulin deficiency and results in type 1 diabetes mellitus (T1DM). The substitution of healthy pancreatic beta cells for damaged cells would be the ideal treatment for T1DM; thus, the generation of pancreatic beta cells from adult stem cells represents an attractive avenue for research. In this study, a cocktail of factors was used to induce the differentiation of pancreatic beta cells from mesenchymal stem cells (MSCs). The differentiation program was divided into five stages, and the roles of the cocktail factors used during each stage were systematically elucidated. Activin A was found to phosphorylate Smad2 and Smad3 in stage III, thereby activating the TGF-β/Smad pathway. Meanwhile, the endocrine-specific transcription factor, Ngn3, and the pancreas-specific miRNAs, miR-375 and miR-26a, were dramatically elevated in stage III. We next demonstrated that Smad4, an important transcription factor in the TGF-β/Smad pathway, could bind to the promoter sequences of target genes and enhance their transcription to initiate the differentiation of beta cells. Use of SB-431542, an inhibitor of the TGF-β/Smad pathway, demonstrated in vivo and in vitro that this pathway plays a critical role in the production of pancreatic beta cells and in modulating insulin secretion. Thus, the TGF-β/Smad pathway is involved in the production of beta cells from adult stem cells by enhancing the transcription of Ngn3, miR-375, and miR-26a. These findings further underline the significant promise of cell transplant therapies for type 1 diabetes mellitus.

MicroRNA (miR)-128-3p is a brain-enriched miRNA that participates in the regulation of neural cell differentiation and the protection of neurons, but the mechanisms by which miR-128-3p regulates its target and downstream genes to influence cell fate from adult stem cells are poorly understood. In this study, we show down-regulation of miR-128-3p during all-trans retinoic acid (ATRA)-induced neurogenic differentiation from amniotic epithelial cells (AECs). We investigated miR-128-3p in both the Notch pathway and in the expression of neuron-specific genes predicted to be involved in miR-128-3p signaling to elucidate its role in the genetic regulation of downstream neurogenic differentiation. Our results demonstrate that miR-128-3p is a negative regulator for the transcription of the neuron-specific genes β III-tubulin, neuron-specific enolase (NSE), and polysialic acid-neural cell adhesion molecule (PSA-NCAM) via targeting Jagged 1 to inhibit activation of the Notch signaling pathway. We also used bioinformatics algorithms to screen for miR-128-3p interactions with long non-coding (lnc) RNA and circular RNA as competing endogenous RNAs to further elucidate underlying down-regulated molecular mechanisms. The lncRNA maternally expressed 3 is up-regulated by the ATRA/cAMP/CREB pathway, and it, in turn, is directly down-regulated by miR-128-3p to increase the amount of neuron differentiation. Endogenous miRNAs are, therefore, involved in neurogenic differentiation from AECs and should be considered during the development of effective cell transplant therapies for the treatment of neurodegenerative disease.

Tumorigenesis is a multistep process involving various cell growth-associated factors. Accumulated evidence indicates that the disordered regulation of microRNAs (miRNAs) contributes to tumorigenesis. However, the detailed mechanism underlying the involvement of miRNAs in oncogenesis remains to be fully elucidated. In the present study, the repressed expression of microRNA (miR)-494 was identified in 18 patients with osteosarcoma (OS) and OS cell lines, compared with corresponding controls. To determine whether deregulated miR-494 exerts tumor-suppressive effects in the development of OS, the effects of miR-494 on cell proliferation and metastasis were evaluated. It was found that the restoration of miR-494 in MG-63 and U2OS cells led to inhibited cell proliferation and attenuated migratory propensity in vitro, determined through analysis using MTT, colony formation and Transwell assays. In addition, overexpression of miR-494 markedly suppressed the tumor volume and weight in vivo. In accordance, the ectopic expression of miR-494 induced cell cycle arrest at the G1/S phase in OS cells. Bioinformatics analysis and luciferase reporter assays were performed to investigate the potential regulatory role of miR-494, the results of which indicated that miR-494 directly targeted cyclin-dependent kinase 6 (CDK6). Of note, the data obtained through reverse transcription-quantitative polymerase chain reaction and western blot analyses suggested that the elevated expression of miR-494 resulted in reduced mRNA and protein expression levels of CDK6. Taken together, these findings indicated that the miR-494/CDK6 axis has a significant tumor-suppressive effect on OS, and maybe a diagnostic and therapeutic target for the treatment of OS. [ABSTRACT FROM AUTHOR]