Hsa_circ_0002111/miR-557/DUSP14 axis mediates euthyrox-resistance in papillary thyroid cancer

  • Jing Zhou The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
  • Jing Liu The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
  • Weiyuan Ma The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
  • Pengxin Zhao The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
Keywords: miR-557, Circ_0002111, Euthyrox resistant, DUSP14, Umael

Abstract

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.

Downloads

Download data is not yet available.

References

Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet 2016; 388: 2783–95. doi: 10.1016/S0140-6736(16)30172-6

Wiltshire JJ, Drake TM, Uttley L, Balasubramanian SP. Systematic review of trends in the incidence rates of thyroid cancer. Thyroid 2016; 26: 1541–52. doi: 10.1089/thy.2016.0100

Mao YS, Xing MZ. Recent incidences and differential trends of thyroid cancer in the USA. Endocr Relat Cancer 2016; 23: 313–22. doi: 10.1530/ERC-15-0445

Aragon Han P, Weng CH, Khawaja HT, Nagarajan N, Schneider EB, Umbricht CB, et al. MicroRNA expression and association with clinicopathologic features in papillary thyroid cancer: a systematic review. Thyroid 2015; 25: 1322–9. doi: 10.1089/thy.2015.0193

Kunavisarut T. Diagnostic biomarkers of differentiated thyroid cancer. Endocrine 2013; 44: 616–22. doi: 10.1007/s12020-013-9974-2

Lundgren CI, Hall P, Dickman PW, Zedenius J. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer 2006; 106: 524–31. doi: 10.1002/cncr.21653

Fiore E, Rago T, Latrofa F, Provenzale MA, Piaggi P, Delitala A, et al. Hashimoto’s thyroiditis is associated with papillary thyroid carcinoma: role of TSH and of treatment with L-thyroxine. Endocr Relat Cancer 2011; 18: 429–37. doi: 10.1530/ERC-11-0028

Han B, Chao J, Yao HH. Circular RNA and its mechanisms in disease: from the bench to the clinic. Pharmacol Ther 2018; 187: 31–44. doi: 10.1016/j.pharmthera.2018.01.010

Nicolet BP, Engels S, Aglialoro F, van den Akker E, von Lindern M, Wolkers MC. Circular RNA expression in human hematopoietic cells is widespread and cell-type specific. Nucleic Acids Res 2018; 46: 8168–80. doi: 10.1093/nar/gky721

Salzman J. Circular RNA Expression: its potential regulation and function. Trends Genet 2016; 32: 309–16. doi: 10.1016/j.tig.2016.03.002

Jin XY, Wang ZY, Pang WY, Zhou J, Liang Y, Yang JJ, et al. Upregulated hsa_circ_0004458 contributes to progression of papillary thyroid carcinoma by inhibition of miR-885-5p and activation of RAC1. Med Sci Monit 2018; 24: 5488–500. doi: 10.12659/MSM.911095

Tian XF, Zhang L, Jiao Y, Chen JS, Shan Y, Yang WF. CircABCB10 promotes nonsmall cell lung cancer cell proliferation and migration by regulating the miR-1252/FOXR2 axis. J Cell Biochem 2019; 120: 3765–72. doi: 10.1002/jcb.27657

Yao Y, Chen XY, Yang H, Chen W, Qian YC, Yan ZY, et al. Hsa_circ_0058124 promotes papillary thyroid cancer tumorigenesis and invasiveness through the NOTCH3/GATAD2A axis. J Exp Clin Cancer Res 2019; 38: 318. doi: 10.1186/s13046-019-1321-x

Li QD, Wang YC, Wu S, Zhou Z, Ding XJ, Shi RH, et al. CircACC1 regulates assembly and activation of AMPK complex under metabolic stress. Cell Metab 2019; 30: 157–73.e7. doi: 10.1016/j.cmet.2019.05.009

Zhao HD, Tang HL, Huang QK, Qiu B, Liu XM, Fan D, et al. MiR-101 targets USP22 to inhibit the tumorigenesis of papillary thyroid carcinoma. Am J Cancer Res 2016; 6: 2575–86.

Wang Z. Editorial (hot topic: miRNAs as legitimate targets for cancer therapy). Curr Drug Targets 2013; 14: 1093. doi: 10.2174/1389450111314100001

Shao H, Zhang Y, Yan J, Ban X, Fan X, Chang X, et al. Upregulated MicroRNA-483-3p is an early event in pancreatic ductal adenocarcinoma (PDAC) and as a powerful liquid biopsy biomarker in PDAC. Onco Targets Ther 2021; 14: 2163–75. doi: 10.2147/OTT.S288936

Panda AC. Circular RNAs act as miRNA sponges. Adv Exp Med Biol 2018; 1087: 67–79. doi: 10.1007/978-981-13-1426-1_6

Qiu J, Hao Y, Huang S, Ma Y, Li X, Li D, et al. MiR-557 works as a tumor suppressor in human lung cancers by negatively regulating LEF1 expression. Tumour Biol 2017; 39: 1010428317709467. doi: 10.1177/1010428317709467

Yang Y, Sun KK, Shen XJ, Wu XY, Li DC. miR-557 inhibits the proliferation and invasion of pancreatic cancer cells by targeting EGFR. Int J Clin Exp Pathol 2019; 12: 1333–41.

Kia V, Paryan M, Mortazavi Y, Biglari A, Mohammadi-Yeganeh S. Evaluation of exosomal miR-9 and miR-155 targeting PTEN and DUSP14 in highly metastatic breast cancer and their effect on low metastatic cells. J Cell Biochem 2019; 120: 5666–76. doi: 10.1002/jcb.27850

Mabrouk NMK, Elkaffash DM, Abdel-Hadi M, Abdelmoneim SE, Saad ElDeen S, Gewaifel G, et al. Identification of the possible therapeutic targets in the insulin-like growth factor 1 receptor pathway in a cohort of Egyptian hepatocellular carcinoma complicating chronic hepatitis C type 4. Drug Target Insights 2020; 14: 1–11. doi: 10.33393/dti.2020.1548

Wei Y, Wang G, Wang C, Zhou Y, Zhang J, Xu K. Upregulation of DUSP14 affects proliferation, invasion and metastasis, potentially via epithelial-mesenchymal transition and is associated with poor prognosis in pancreatic cancer. Cancer Manag Res 2020; 12: 2097–108. doi: 10.2147/CMAR.S240040

Yan F, Ying L, Li X, Qiao B, Meng Q, Yu L, et al. Overexpression of the transcription factor ATF3 with a regulatory molecular signature associates with the pathogenic development of colorectal cancer. Oncotarget 2017; 8: 47020–36. doi: 10.18632/oncotarget.16638

Ashraf S, Hegazy YK, Harmancey R. Nuclear receptor subfamily 4 group A member 2 inhibits activation of ERK signaling and cell growth in response to beta-adrenergic stimulation in adult rat cardiomyocytes. Am J Physiol Cell Physiol 2019; 317: C513–24. doi: 10.1152/ajpcell.00526.2018

Douglas T, Saleh M. Post-translational modification of OTULIN regulates ubiquitin dynamics and cell death. Cell Rep 2019; 29: 3652–63.e5. doi: 10.1016/j.celrep.2019.11.014

Jianrong S, Yanjun Z, Chen Y, Jianwen X. DUSP14 rescues cerebral ischemia/reperfusion (IR) injury by reducing inflammation and apoptosis via the activation of Nrf-2. Biochem Biophys Res Commun 2019; 509: 713–21. doi: 10.1016/j.bbrc.2018.12.170

Published
2022-04-04
How to Cite
ZhouJ., LiuJ., MaW., & ZhaoP. (2022). Hsa_circ_0002111/miR-557/DUSP14 axis mediates euthyrox-resistance in papillary thyroid cancer. STEMedicine, 3(2), e127. https://doi.org/10.37175/stemedicine.v3i2.127
Section
Research articles