ABSTRACT
OBJECTIVE: The goal of this study was to investigate the status of FEN1 in colorectal cancer (CRC) and determine the potential correlation between FEN1 expression level and clinicopathological parameters in CRC patients. METHODS: Expression of FEN1 in CRC tissue on tissue microarray was detected using immunohistochemistry (IHC). The relationship between FEN1 expression status and clinicopathologic characteristics of CRC was analyzed by the Chi-square test. The survival data of TCGA Colon Cancer (COAD) were obtained from ucsc xena browser (https://xenabrowser.net/). Patients were separated into higher and lower expression groups by median FEN1 expression. The association with prognosis of CRC patients was determined by Kaplan-Meier survival analysis with Log-rank test. RESULTS: FEN1expression level and cellular localization had wide variability among different individuals; we classified the staining results into four types: both positive in nucleus and cytoplasm, both negative in nucleus and cytoplasm, only positive in the nucleus, only positive in the cytoplasm. Moreover, FEN1 expression status only correlated with patient's metastasis status, and the patients in the NLCL group showed more risk of cancer cell metastasis. CONCLUSION: Our results indicate that FEN1 expression level and cellular localization had wide variability in CRC and is not a promising biomarker in CRC.
Subject(s)
Colorectal Neoplasms , Biomarkers , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Flap Endonucleases , Humans , Kaplan-Meier EstimateABSTRACT
BACKGROUND: The tumour microenvironment contributes to chemotherapy resistance in gliomas, and glioma-associated mesenchymal stromal/stem cells (gaMSCs) are important stromal cell components that play multiple roles in tumour progression. However, whether gaMSCs affect chemotherapy resistance to the first-line agent temozolomide (TMZ) remains unclear. Herein, we explored the effect and mechanism of gaMSCs on resistance to TMZ in glioma cells. METHODS: Human glioma cells (cell line U87MG and primary glioblastoma cell line GBM-1) were cultured in conditioned media of gaMSCs and further treated with TMZ. The proliferation, apoptosis and migration of glioma cells were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and wound-healing assays. The expression of FOXS1 in glioma cells was analysed by gene microarray, PCR and Western blotting. Then, FOXS1 expression in glioma cells was up- and downregulated by lentivirus transfection, and markers of the epithelial-mesenchymal transformation (EMT) process were detected. Tumour-bearing nude mice were established with different glioma cells and treated with TMZ to measure tumour size, survival time and Ki-67 expression. Finally, the expression of IL-6 in gaMSC subpopulations and its effects on FOXS1 expression in glioma cells were also investigated. RESULTS: Conditioned media of gaMSCs promoted the proliferation, migration and chemotherapy resistance of glioma cells. The increased expression of FOXS1 and activation of the EMT process in glioma cells under gaMSC-conditioned media were detected. The relationship of FOXS1, EMT and chemotherapy resistance in glioma cells was demonstrated through the regulation of FOXS1 expression in vitro and in vivo. Moreover, FOXS1 expression in glioma cells was increased by secretion of IL-6 mainly from the CD90low gaMSC subpopulation. CONCLUSIONS: CD90low gaMSCs could increase FOXS1 expression in glioma cells by IL-6 secretion, thereby activating epithelial-mesenchymal transition and resistance to TMZ in glioma cells. These results indicate a new role of gaMSCs in chemotherapy resistance and provide novel therapeutic targets.
Subject(s)
Brain Neoplasms , Glioma , Animals , Apoptosis , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm/genetics , Epithelial-Mesenchymal Transition , Glioma/drug therapy , Glioma/genetics , Mice , Mice, Nude , Stem Cells , Temozolomide/pharmacology , Tumor MicroenvironmentABSTRACT
BACKGROUND: Cervical cancer is one of the most common causes of cancer-associated mortality among affected women in the world. At present, treatment with weekly cisplatin plus ionizing radiation (IR) therapy is the standard regimen for cervical cancer, especially for locally advanced cervical cancer. The purpose of this study is to determine whether FEN1 inhibitors could enhance the therapeutic effect of IR therapy. METHODS: Western blot was applied to determine the expression of FEN1- and apoptosis-related proteins. Cell growth inhibition assay and colony formation assay were used to determine the effects of FEN1 inhibitor and IR exposure for Hela cells in vitro. CRISPR technology was used to knockdown FEN1 expression level of 293T cells, and tumor xenograft in nude mice was employed to determine the effects of FEN1 inhibitor and IR exposure on tumor growth in vivo. RESULTS: Our data revealed that FEN1 is overexpressed in HeLa cell and can be upregulated further by IR. We also demonstrated that FEN1 inhibitor enhances IR sensitivity of cervical cancer in vitro and in vivo. CONCLUSION: FEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell.
Subject(s)
Enzyme Inhibitors/pharmacology , Flap Endonucleases/antagonists & inhibitors , Radiation Tolerance/drug effects , Radiation-Sensitizing Agents/pharmacology , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Disease Models, Animal , Female , Flap Endonucleases/genetics , Flap Endonucleases/metabolism , Gene Expression , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , HeLa Cells , Humans , Mice , Radiation, Ionizing , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
DNA-functionalized nanoparticle (DfNP) technology, the integration of DNA with nanotechnology, has emerged over recent decades as a promising biofunctionalization tool in the light of biotechnological approaches. The development of DfNPs has exhibited significant potential for several biological and biomedical applications. In this review, we focus on the mechanism of a series of DNA-NP nanocomposites and highlight the superstructures of DNA-based NPs. We also summarize the applications of these nanocomposites in cell imaging, cancer therapy and bioanalytical detection.
Subject(s)
Biotechnology , DNA/chemistry , Nanoparticles/chemistry , Nanotechnology , Animals , HumansABSTRACT
Human glioma-associated mesenchymal stem cells (gbMSCs) are the stromal cell components that contribute to the tumourigenesis of malignant gliomas. Recent studies have shown that gbMSCs consist of two distinct subpopulations (CD90+ and CD90- gbMSCs). However, the different roles in glioma progression have not been expounded. In this study, we found that the different roles of gbMSCs in glioma progression were associated with CD90 expression. CD90high gbMSCs significantly drove glioma progression mainly by increasing proliferation, migration and adhesion, where as CD90low gbMSCs contributed to glioma progression chiefly through the transition to pericytes and stimulation of vascular formation via vascular endothelial cells. Furthermore, discrepancies in long non-coding RNAs and mRNAs expression were verified in these two gbMSC subpopulations, and the potential underlying molecular mechanism was discussed. Our data confirm for the first time that CD90high and CD90low gbMSCs play different roles in human glioma progression. These results provide new insights into the possible future use of strategies targeting gbMSC subpopulations in glioma patients.
Subject(s)
Brain Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Glioma/genetics , Mesenchymal Stem Cells/metabolism , Thy-1 Antigens/genetics , Adipocytes/metabolism , Adipocytes/pathology , Adult , Aged , Animals , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Cell Adhesion , Cell Differentiation , Cell Line, Tumor , Cell Movement , Cell Proliferation , Chondrocytes/metabolism , Chondrocytes/pathology , Female , Glioma/mortality , Glioma/pathology , Glioma/surgery , Humans , Male , Mesenchymal Stem Cells/pathology , Mice, Nude , Middle Aged , Neoplasm Grading , Neoplasm Transplantation , Osteoblasts/metabolism , Osteoblasts/pathology , Primary Cell Culture , Signal Transduction , Survival Analysis , Thy-1 Antigens/metabolismABSTRACT
Porcine circovirus type 2(PCV2) recently emerged as an important infectious pathogen for pigs in the world. Unfortunately, there is no efficient method to deal with PCV2 infection until now. In this study, chimeric porcine circovirus molecular clone (pSK2PCV1-2) was constructed by cloning capsid gene of PCV2 into the backbone of PCV1. PK-15 cells was transfected with pSK2PCV1-2 and then cultivated in plate for five passages. mRNA of PCV1 ORF1 and PCV2 ORF2 were detected in the fifth passage, but mRNA of PCV1 ORF2 and PCV2 ORF1 were not detected in the cells. On the other hand, capsid protein of PCV2 was also detected in the nucleolus of transfected cells by IIF. This study indicated that pSK2PCV1-2 could form infectious virus in transfected cells. It will provide base for further study on biological characteristic of chimeric porcine circovirus.
