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Objective To investigate the molecular mechanism of histone demethylase 5C (KDM5C) regulating human cervical carcinogenesis through Hippo-YAP1 pathway. Methods Using CaSki cell lines stably overexpressing KDM5C protein, whole transcriptome sequencing was performed by RNA-Seq technique, and differentially expressed genes were analyzed, and then GO analysis, KEGG analysis and protein interaction network analysis were performed on these differential genes. After that, siRNA knocked down KDM5C and reversely verified the expression changes of key regulated gene Yes associate protein 1 (YAP1) by RT-qPCR and Western blotting. Meanwhile, in CaSki cell lines, the effect of KDM5C protein overexpression on the methylation status of YAP1 gene promoter region was analyzed by chromatin immunoprecipitation sequencing (ChIP-Seq) and ChIP-qPCR methods. Results RNA-Seq analysis showed that overexpression of KDM5C significantly up-regulated expressions of 356 mRNAs and down-regulated 335 mRNAs expressions (P<0.05). GO enrichment analysis showed that KDM5C protein was mainly involved in various biological development processes of the body. KEGG enrichment analysis showed that KDM5C protein was mainly involved in focal adhesion, steroid hormone biosynthesis, Hippo-YAP1 pathway, FoxO pathway, apoptosis and infection. Further RT-qPCR analysis showed that knockdown of KDM5C with gene specific siRNAs could up-regulate the expression of YAP1, and Western blotting results also confirmed that reduction the expression of KDM5C protein could up-regulate the levels of YAP1 and phosphorylated YAP1 simultaneously (P<0.05). ChIP-Seq analysis showed that KDM5C overexpression cell line could significantly increase the H3K4me1 level and decrease the H3K4me3 level in the promoter interval of YAP1 gene compared with the control cell line, and this expression change was also verified by subsequent ChIP-qPCR (P<0.05). Conclusions The KDM5C protein regulates the methylation level of the histone H3K4me1/me3 in the YAP1 gene promoter of cervical cancer cells, thereby affecting the transcription of the YAP1 gene. As a core factor in Hippo-YAP1 pathway, the expression of YAP1 protein directly affects cell adhesion, proliferation, and apoptosis, thereby participating in the occurrence and development of cervical cancer.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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