Int J Med Sci
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Increasing evidence has demonstrated that circular RNA (circRNA) exerts important function in the pathogenesis of some diseases. While, the contributions of circRNAs to aseptic loosening after total hip arthroplasty (THA) remain largely unknown. Our research is to explore the differentially expressed circRNAs (DEcircRNAs) and elucidate complex regulated mechanism of circRNAs in aseptic loosening. ⋯ Then, circRNA-miRNA-mRNA network was established. The result of GO and KEGG enrichment analysis suggested that the circRNAs were related with some biological functions and pathways of aseptic loosening. A novel pathogenesis and treatment strategy about aseptic loosening after THA was revealed from our study of circRNA-miRNA-mRNA network.
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Background: The cell division cycle-associated (CDCA) protein family plays a pivotal role in the regulation of the cell cycle during tumorigenesis and predicts the prognosis of tumors, but an analysis of these proteins in pancreatic adenocarcinoma (PAAD) is still lacking. Methods: Oncomine and GEPIA were used to observe the expression and prognostic value of eight CDCAs in pan-cancer. Univariate Cox analysis of single CDCAs and multivariate Cox analysis of all eight CDCAs were performed to evaluate the integrated prognostic value of CDCAs, and the results are displayed as hazard ratios (HRs) and 95% confidence intervals (95% CIs). ⋯ After comparing high- and low-risk groups separated by CDCA risk scores, the activated pathways were revealed and included the cell cycle, DNA repair, P53, MYC-targets, E2F-targets and PI3K pathways. Conclusion: CDCAs can predict the OS prognosis of PAAD patients. The cell cycle, DNA repair, E2F, P53 and PI3K signaling pathways, in which CDCAs are involved, impact the tumorigenesis of PAAD.
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Objective: Fhit gene is known as a genome "caretaker" and frequently inactivated by deletion or hypermethylation on the promoter in several cancers. In spite of several lines of evidence, the exact mechanism underlying Fhit-induced biology is relatively less studied. This study will focus the role of Fhit in regulating Lin28 and microRNAs (miRNAs) loop. ⋯ Also, we found that miRNAs in miR-17/92 clusters are redundantly increased and there is an inverse correlation between Let-7 and miR-17/92 clusters in Fhit-expressing cells. Also, a series of in vitro experiments suggests that ELF-1- and/or STAT1-dependent Lin28b regulation is responsible for Let-7 induction in Fhit-expressing cancer cells. Conclusions: Based on the same experimental system proving that Fhit gene has a robust role in suppressing tumor progression and epithelial-mesenchymal transition, our data show that Fhit mediates the negative feedback between Lin28/Let-7 axis and miR-17/-92 miRNA although the physiological relevance of current interesting observation should be further investigated.
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The function of the uncoupling protein 2 (UCP2) is different for each cancer cell. However, the mechanism of expression is still unclear. DNA methylation affects protein expression and is one factor that transforms normal cells into cancer cells. ⋯ The UCP2 promoter in Hep3B cells has numerous methylated regions compared with HT-29 and HepG2 cells. The results of the present study revealed that inhibition of UCP2 expression in Hep3B cells was due to methylation of the promoter region. Investigating the mechanism that induces UCP2 expression in cancer cells is important to understand the function of UCP2, which could aid in cancer treatment.
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Malignant gliomas are a type of central nervous system cancer with extremely high mortality rates in humans. γ-secretase has been becoming a potential target for cancer therapy, including glioma, because of the involvement of its enzymatic activity in regulating the proliferation and metastasis of cancer cells. In this study, we attempted to determine whether γ-secretase activity regulates E-cadherin to affect glioma cell migration. The human glioma cell lines, including LN18 and LN229, and the γ-secretase inhibitors, including N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) and RO4929097, were used in this study. ⋯ Moreover, endogenous Smad1 in glioma cells was found to play an important role in regulating E-cadherin expression and subsequent cell migration but did not affect DAPT-stimulated effects. These results help further elucidate the molecular mechanisms of γ-secretase activity regulation involved in controlling glioma cell malignancy. Information about a potential role for Smad1/5 activity upregulation and subsequent E-cadherin downregulation during inhibition of γ-secretase activity in the development of gliomas is therefore relevant for future research.