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作 者:Meng Xu Anyi Cheng Liya Yu Wei Wei Jinpeng Li Cheguo Cai
机构地区:[1]Department of Thyroid and Breast Surgery,Zhongnan Hospital of Wuhan University,Medical Research Institute,Frontier Science Center for Immunology and Metabolism,Wuhan University,Wuhan 430071,China [2]Department of Thyroid and Breast Surgery,Zhongnan Hospital of Wuhan University,Wuhan 430071,China
出 处:《Acta Biochimica et Biophysica Sinica》2022年第11期1708-1719,共12页生物化学与生物物理学报(英文版)
基 金:This work was supported by the grants from the Ministry of Science and Technology of China(No.2019YFA0802804);the National Natural Science Foundation of China(Nos.31671546 and 31871492)。
摘 要:Adenocarcinoma is the second largest histological type of cervical cancer,second only to cervical squamous cell carcinoma.At present,despite the clinical treatment strategies of cervical adenocarcinoma and cervical squamous cell carcinoma being similar,the outcome and prognosis of cervical adenocarcinoma are significantly poor.Therefore,it is urgent to find specific biomarker and therapeutic target for cervical adenocarcinoma.In this study,we aim to reveal and verify the potential biomarkers and therapeutic targets of cervical adenocarcinoma.Weighted correlation network analysis(WGCNA)reveals the differentially-expressed genes significantly related to the histological characteristics of the two cervical cancer subtypes.We select the genes with the top 20 significance for further investigation.Through microarray and immunohistochemical(IHC)analyses of a variety of tumor tissues,we find that among these 20 genes,AHNAK2 is highly expressed not only in cervical adenocarcinoma,but also in multiple of adenocarcinoma tissues,including esophagus,breast and colon,while not in normal gland tissues.In vitro,AHNAK2 knockdown significantly inhibits cell proliferation and migration of adenocarcinoma cell lines.In vivo,AHNAK2 knockdown significantly inhibits tumor progression and metastasis of various adenocarcinomas.RNA-sequencing and bioinformatics analyses suggest that the inhibitory effect of AHNAK2 knockdown on tumor progression is achieved by regulating DNA replication and upregulating Bim expression.Together,we demonstrate that AHNAK2 is a biomarker and a potential therapeutic target for adenocarcinomas.
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