AHNAK2 is a biomarker and a potential therapeutic target of adenocarcinomas

• Published in: Acta biochimica et biophysica Sinica 2022-11, Vol.54 (11), p.1708-1719
• Main Authors: Xu, Meng, Cheng, Anyi, Yu, Liya, Wei, Wei, Li, Jinpeng, Cai, Cheguo
• Format: Article
• Language: English
• Subjects: adenocarcinoma; Adenocarcinoma - drug therapy; AHNAK2; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Female; Humans; Molecular Targeted Therapy; squamous carcinoma; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; WGCNA
• ISSN: 1672-9145; 1745-7270
• DOI: 10.3724/abbs.2022112

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.