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

Aims: 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 () was significantly upregulated in the thyroid cancer patient's tissue.

Methods: We also analyzed mRNA levels of DTC tissues and normal tissues from The Cancer Genome Atlas (TCGA). The association between the expression level of and clinicopathological features was evaluated in the TCGA cohort. Furthermore, 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 . For cell experiments in vitro, was knocked down using small interfering RNA (siRNA), and the biological function of in TC cell lines was investigated. The expression of 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 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 might be considered a diagnostic biomarker for TC. The knockdown of 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 may promote metastasis and proliferation of thyroid cancer through PI3K/AKT signaling pathway. Thus, may be used as a candidate marker for TC diagnosis and treatment.