CircNDST1 promotes papillary thyroid cancer progression via its interaction with CSNK2A1 to activate the PI3K-Akt pathway and epithelial-mesenchymal transition

Background: Multiple studies have established a strong relationship between circRNA and Cancer progression. Cervical lymph node metastasis is a key factor influencing the surgical approach and distant metastasis of papillary thyroid Cancer (PTC). However, the role of circNDST1 in PTC has not been investigated. Our research focused on revealing the function and mechanism of action of circNDST1 in PTC.

Methods: High-throughput Sequencing and qPCR were used to assess the expression of circRNA in PTC tissues with extensive cervical lymph node metastasis and circNDST1 in cell lines, respectively. The proliferative effects of circNDST1 in vitro and in vivo were analyzed using CCK8, clone formation assay, EdU, and nude mouse tumorigenesis assay. The transwell scratch assay was employed in the scrutiny of the effect of circNDST1 on the migration and invasion abilities of thyroid Cancer cells, while circNDST1's influence on the PI3K-Akt pathway and the Epithelial-Mesenchymal Transition (EMT) key protein expression was evaluated utilizing RNA Sequencing and western blot. RNA pull-down and RIP were used to examine the binding of circNDST1 to CSNK2A1.

Results: CircNDST1 was highly expressed in PTC cell lines, but knocking it down inhibited the proliferation, migration, and invasive abilities of TPC1 and KTC1 cell lines. CircNDST1 bonded with CSNK2A1 and promoted the interaction between CSNK2A1 and Akt, leading to the activation of the PI3K-Akt pathway and EMT.

Conclusion: CircNDST1's high expression boosted thyroid Cancer progression through the activation of the PI3K-Akt pathway and EMT in a CSNK2A1-dependent manner.

EMT; PI3K–Akt pathway; Thyroid cancer; circNDST1.