Research Paper Volume 10, Issue 12 pp 3806—3820

Circular RNA EIF6 (Hsa_circ_0060060) sponges miR-144-3p to promote the cisplatin-resistance of human thyroid carcinoma cells by autophagy regulation

Feng Liu 1, *, , Jin Zhang 2, *, , Long Qin 3, , Ziyao Yang 3, , Jianxia Xiong 3, , Yanyan Zhang 2, , Ruihuan Li 2, , Shujing Li 2, , Huifang Wang 3, , Bo Yu 3, , Wenjun Zhao 3, , Weiran Wang 4, , Zhensu Li 2, , Jing Liu 2, ,

  • 1 Department of Forensic Medicine, Shanxi Medical University, Taiyua, Shanxi 030001, China
  • 2 Department of General Surgery, First Hospital of Shanxi Medical University, Taiyua, Shanxi 030001, China
  • 3 Department of General Surgery, First Clinical Medical College of Shanxi Medical University, Taiyua, Shanxi 030001, China
  • 4 Department of General Surgery, Second Clinical Medical College of Shanxi Medical University, Taiyua, Shanxi 030001, China
* Equal contribution

received: August 13, 2018 ; accepted: November 15, 2018 ; published: December 12, 2018 ;

https://doi.org/10.18632/aging.101674
How to Cite

Copyright: Liu et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Anaplastic thyroid carcinoma (ATC) responds for the majority of death of thyroid carcinoma and often causes chemotherapy resistance. We investigated the influence of circEIF6 (Hsa_circ_0060060) on the cisplatin-sensitivity in papillary thyroid carcinoma (PTC) and ATC cells, and explored its regulation to downstream molecules miR-144-3p and Transforming Growth Factor α (TGF-α). Differentially expressed circRNAs in PTC were analyzed using the GSE93522 data downloaded. Expressions of circEIF6, miR-144-3p, TGF-α, autophagy-related proteins and apoptosis-related proteins were determined using qRT-PCR or western blot. RNA pull-down assay and dual luciferase report assay were applied to reveal the target relationships. Autophagy marker LC3 and cell proliferation marker ki67 were evaluated by immunofluorescence and immunohistochemistry. Cell viability was evaluated with MTT assay and cell apoptosis was assessed by flow cytometric analysis. CircEIF6, could promote autophagy induced by cisplatin, thus inhibiting cell apoptosis and enhancing the resistance of PTC and ATC cells to cisplatin. Has-miR-144-3p was the target of circEIF6 and was regulated by circEIF6. Besides, circEIF6 promoted autophagy by regulating miR-144-3p/TGF-α axis, enhancing the cisplatin-resistance in PTC and ATC cells. CircEIF6 promoted tumor growth by regulating miR-144-3p/TGF-α and circEIF6 knock-down enhanced cisplatin sensitivity in vivo. CircEIF6 could provide a target for therapy of cisplatin-resistance in thyroid carcinoma.

Abbreviations

ATC: Anaplastic thyroid carcinoma; DMSO: dimethyl sulfoxide; EMT: epithelial-mesenchymal transition; GFP: green fluorescent protein; HBx: hepatitis B viral X; HRP: horseradish peroxidase; MKIs: multi kinase inhibitors; MTC: medullary thyroid carcinoma; PTC: papillary thyroid carcinoma; PVDF: polyvinylidene fluoride; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; TGF-α: Transforming Growth Factor α.