Open AccessHsa_circ_0002111/miR-557/DUSP14 axis mediates euthyrox-resistance in papillary thyroid cancer
Author(s) -
Jing Zhou,
Jing Liu,
Wenxue Ma,
Pengxin Zhao
Publication year - 2022
Publication title -
stemedicine
Language(s) - English
Resource type - Journals
ISSN - 2705-1188
DOI - 10.37175/stemedicine.v3i2.127
Subject(s) - cancer research , downregulation and upregulation , apoptosis , thyroid cancer , viability assay , cell culture , papillary thyroid cancer , thyroid carcinoma , chemistry , cancer , microbiology and biotechnology , medicine , biology , thyroid , gene , biochemistry , genetics
As one of the most commonly used chemotherapeutic drug for papillary thyroid cancer (PTC), euthyrox affects the therapeutic outcome due to the resistance of euthyrox. Hsa_circ_0002111 is highly expressed in euthyrox-resistant PTC patients, and this study intends to explore its role in euthyrox drug resistance. PTC patient samples were used to screen for Circ_0002111 expression. TPC-1 and K1 PTC cell lines and their corresponding euthyrox-resistant cell lines (TPC-1/euthyrox and K1/euthyrox), and a benign human thyroid follicular cell line (Nthy-ori 3-1) were used in in vitro experiments. Circ_0002111 was knocked down in euthyrox-resistant cell lines, and cell viability and colony formation were detected. Caspase-3 activity assay and nucleosomal fragmentation assay were used for the detection of apoptosis. Luciferase reporter assay and biotin-labeled RNA pulldown assay were used to analyze interactions between Circ_0002111 and miR-557, or miR-557 and DUSP14. The upregulation of Circ_0002111 was found in PTC patient samples and associated with euthyrox-resistance in poor prognosis of PTC patients. Experiments in cell lines showed that Circ_0002111 regulates euthyrox-resistance in PTC cells. Mechanistic studies showed that Circ_0002111 promoted DUSP14 expression through miR-557, and euthyrox-resistance in PTC cells depended on the regulation via miR-557/DUSP14 signaling pathways. In conclusion, Hsa_circ_0002111 promotes euthyrox-resistance of PTC cells by adsorption miR-557 upregulation, suggesting Circ_0002111 might be a potential diagnostic marker and therapeutic target for euthyrox-resistant PTC patients.