Potential mechanisms underlying the promoting effects of 3D collagen scaffold culture on stemness and drug resistance of glioma cells |
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| Institution: | 1. Cancer Research Institute, Department of Neurosurgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China;2. Medical College of Jishou University, Jishou City, Hunan 416000, China;3. The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China;4. Changsha Kexin Cancer Hospital, Changsha, Hunan 410000, China;5. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China;6. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China |
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| Abstract: | Background3D collagen scaffold culture is a good tool to study glioma metastasis and recurrence in vitro.MethodsThe effect of 3D collagen culture on the colony formation, the sphere formation, and drug sensitivity of glioma cells was observed by soft-agar colony formation assays, sphere formation assays, and CCK-8 assays, respectively. 3D-glioma-drug genes were identified by previous results and online databases. Gene enrichment and PPI analyses were performed by R software and Metacsape. Hub 3D-glioma-drug genes were screened by STRING and Cytoscape. TCGA and CGGA databases and R software were used to analyze the distribution of hub genes in glioma and their effects on the prognosis. Western Blot was used to verify the effect of 3D collagen culture on the expression of hub genes. miRNAs targeting hub genes were predicted by ENCORI.Results3D collagen scaffold culture promoted colony formation, sphere formation, and drug resistance of glioma cells. There were 77 3D-glioma-drug genes screened, and the pathways enriched in the protein interaction network mainly included responses to stressors, DNA damage and repair, and drug metabolism. Hub 3D-glioma-drug genes were AKT1, ATM, CASP3, CCND1, EGFR, PARP1, and TP53. These genes and predicted miRNAs were expressed differentially in glioma samples and partially affected the prognosis of patients with glioma. These findings suggested these hub genes and miRNAs may play a key role in the effects generated by the 3D culture model and become new markers for glioma diagnosis and treatment. |
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| Keywords: | ANOVA"} {"#name":"keyword" "$":{"id":"kw2005"} "$$":[{"#name":"text" "_":"one-way analysis of variance DEGs"} {"#name":"keyword" "$":{"id":"kw4005"} "$$":[{"#name":"text" "_":"differentially expressed genes PPI"} {"#name":"keyword" "$":{"id":"kw6005"} "$$":[{"#name":"text" "_":"protein-protein interaction TCGA"} {"#name":"keyword" "$":{"id":"kw8005"} "$$":[{"#name":"text" "_":"The Cancer Genome Atlas CGGA"} {"#name":"keyword" "$":{"id":"kw1105"} "$$":[{"#name":"text" "_":"Chinese Glioma Genome Atlas LGG"} {"#name":"keyword" "$":{"id":"kw1305"} "$$":[{"#name":"text" "_":"low-grade glioma GBM"} {"#name":"keyword" "$":{"id":"kw1505"} "$$":[{"#name":"text" "_":"glioblastoma ENCORI"} {"#name":"keyword" "$":{"id":"kw1705"} "$$":[{"#name":"text" "_":"Encyclopedia of RNA Interactomes TMZ"} {"#name":"keyword" "$":{"id":"kw1905"} "$$":[{"#name":"text" "_":"temozolomide MCODE"} {"#name":"keyword" "$":{"id":"kw2205"} "$$":[{"#name":"text" "_":"molecular complex detection |
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