ZNF217 Mediates Transcriptional Activation of GRHL3 to Regulate SLC22A31 and Promote Malignant Progression in Thyroid Cancer.

Abstract

The incidence of thyroid cancer (THCA) has increased worldwide during the past 40 years. However, an understanding of the mechanisms and major transcription factors involved in THCA is insufficient to identify therapeutic targets against THCA. To reveal such mechanisms, we conducted bioinformatics analyses to assess the differential expression in human THCA sample and normal tissue sample, leading us to focus on the function of the ZNF217/GRHL3/ SLC22A31 axis in mediating biological activity in THCA. The genes of interest were interfered with lentiviral vectors, and transfection efficiency was verified using RT-qPCR. ZNF217, GRHL3, and SLC22A31 were abundantly expressed in THCA tissues or cells. Knockdown of GRHL3, ZNF217, or SLC22A31 all significantly curtailed the malignant biological behavior of THCA cells. ZNF217 promoted GRHL3 expression through transcriptional activation, thereby increasing the transcription of SLC22A31. Ectopic expression of GRHL3 or SLC22A31 abated the suppressing impact of ZNF217 or GRHL3 knockdown on the biological activity of THCA cells. Collectively, our results demonstrated that ZNF217 acted as an activator of GRHL3, thereby promoting the expression of SLC22A31 and the malignant activity of THCA cells.