Vital and Distinct Roles of H2A.Z Isoforms in Hepatocellular Carcinoma

Autor:	Huan Huang, Hongyu Tao, Yuting Tao, Shaomei Tang, Xiaoliang Huang, Xi Wang, Qiuyan Wang, Liwen Qin, Xian-Guo Zhou
Rok vydání:	2020
Předmět:	0301 basic medicine Gene isoform Spliceosome biology Cell growth Spindle midzone Alternative splicing medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Histone Oncology 030220 oncology & carcinogenesis biology.protein medicine Cancer research Pharmacology (medical) Liver cancer Gene
Zdroj:	OncoTargets and Therapy. 13:4319-4337
ISSN:	1178-6930
DOI:	10.2147/ott.s243823
Popis:	Purpose H2A.Z is an oncogenic histone variant that is overexpressed in cancers. Two isoforms of H2A.Z, H2AFZ and H2AFV, are identical except for a three-amino acid difference. However, their isoform-specific functions remain unclear in cancer development. Thereby, this study aimed to investigate whether the two isoforms play distinct functions in hepatocarcinogenesis. Materials and Methods Expressions of H2A.Z isoforms in 116 paired hepatocellular cancerous and para-cancerous tissues were detected by employing qPCR. GEO and TCGA databases were used to probe expressions and prognostic value of the two H2A.Z isoforms. A comprehensive meta-analysis was conducted. Furthermore, co-expressed analysis of H2AFZ and H2AFV was performed by using cBioPortal database. H2A.Z binding genes from Chip-seq were intersected with H2A.Z isoforms co-expressed genes to perform functional annotations. Cell proliferation experiments from H2AFZ knockout HepG2 and BEL-7402 cells were implemented. Finally, RNA-seq was applied to analyse alternative splicing in H2AFZ knockout and wild-type cells. Results H2AFZ and H2AFV were both significantly upregulated (P < 0.01) in hepatocellular carcinoma and related to poor prognosis (P < 0.01). The two H2A.Z isoforms played vital roles in cell proliferation. It is also predicted that unique functions of H2AFV contain spindle midzone and microtubule, while H2AFZ is especially associated with RNA export and spliceosome. Further, devoid H2AFZ may restrain liver cancer cell proliferation and cause many alternative splicing events. Conclusion Both H2A.Z isoforms play vital and distinct roles in the occurrence and progression of liver cancer, which may pave a way for novel therapeutic applications for cancers in the future.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::b70a9c0548e0451c83525c5c1da60106 https://doi.org/10.2147/ott.s243823 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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