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AHNAK2 是腺癌的生物标志物和潜在治疗靶点。

AHNAK2 is a biomarker and a potential therapeutic target of adenocarcinomas.

机构信息

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.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2022 Aug 25;54(11):1708-1719. doi: 10.3724/abbs.2022112.

Abstract

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, 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. , knockdown significantly inhibits cell proliferation and migration of adenocarcinoma cell lines. , knockdown significantly inhibits tumor progression and metastasis of various adenocarcinomas. RNA-sequencing and bioinformatics analyses suggest that the inhibitory effect of 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.

摘要

腺癌是宫颈癌的第二大组织学类型,仅次于宫颈鳞状细胞癌。目前,尽管宫颈腺癌和宫颈鳞状细胞癌的临床治疗策略相似,但宫颈腺癌的结局和预后明显较差。因此,迫切需要找到针对宫颈腺癌的特异性生物标志物和治疗靶点。在这项研究中,我们旨在揭示和验证宫颈腺癌的潜在生物标志物和治疗靶点。加权相关网络分析(WGCNA)揭示了与两种宫颈癌亚型组织学特征显著相关的差异表达基因。我们选择了前 20 个具有重要意义的基因进行进一步研究。通过对多种肿瘤组织的微阵列和免疫组织化学(IHC)分析,我们发现这 20 个基因中,AHNAK2 不仅在宫颈腺癌中高度表达,而且在食管、乳腺和结肠等多种腺癌组织中也高度表达,而在正常腺体组织中不表达。AHNAK2 敲低显著抑制腺癌细胞系的增殖和迁移。AHNAK2 敲低显著抑制各种腺癌的肿瘤进展和转移。RNA-seq 和生物信息学分析表明,AHNAK2 敲低对肿瘤进展的抑制作用是通过调节 DNA 复制和上调 Bim 表达来实现的。综上所述,我们证实 AHNAK2 是腺癌的一个生物标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/9828698/7fad11b117ca/ABBS-2022-074-t1.jpg

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