AHNAK2 Promotes the Progression of Differentiated Thyroid Cancer through PI3K/AKT Signaling Pathway

Aims: AHNAK2 may be used as a candidate marker for TC diagnosis and treatment. Background: Thyroid cancer [TC] is the most frequent malignancy in endocrine carcinoma, and the incidence has been increasing for decades. Objective: To understand the molecular mechanism of DTC, we performed next-generation sequencing [NGS] on 79 paired DTC tissues and normal thyroid tissues. The RNA-sequencing [RNA-seq] data analysis results indicated that AHNAK nucleoprotein 2 [AHNAK2] was significantly upregulated in the thyroid cancer patient’s tissue. Methods: We also analyzed AHNAK2 mRNA levels of DTC tissues and normal tissues from The Cancer Genome Atlas [TCGA]. The association between the expression level of AHNAK2 and clinicopathological features was evaluated in the TCGA cohort. Furthermore, AHNAK2 gene expression was analyzed by quantitative real-time polymerase chain reaction [qRT-PCR] in 40 paired DTC tissues and adjacent normal thyroid tissues. The receiver operating characteristic [ROC] curve was performed to evaluate the diagnostic value of AHNAK2. For cell experiments in vitro, AHNAK2 was knocked down using small interfering RNA [siRNA], and the biological function of AHNAK2 in TC cell lines was investigated. The expression of AHNAK2 was significantly upregulated in both the TCGA cohort and the local cohort. Results: The analysis results of the TCGA cohort indicated that the upregulation of AHNAK2 was associated with tumor size [P<0.001], lymph node metastasis [P<0.001], and disease stage [P<0.001]. The area under the curve [AUC, TCGA: P<0.0001; local validated cohort: P<0.0001.] in the ROC curve revealed that AHNAK2 might be considered a diagnostic biomarker for TC. The knockdown of AHNAK2 reduced TC cell proliferation, colony formation, migration, invasion, cell cycle, and induced cell apoptosis Conclusion: Furthermore, the protein levels of phospho-PI3 Kinase p85 and phospho-AKT were downregulated in the transfected TC cell. Our study results indicate that AHNAK2 may promote metastasis and proliferation of thyroid cancer through PI3K/AKT signaling pathway. Thus, AHNAK2 may be used as a candidate marker for TC diagnosis and treatment.