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

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.

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

“…CircATP8B4 was demonstrated to promote glioma radioresistance by serving as a miR-766 sponge, and circATP8B4 in EVs may be a potential biomarker for glioma radioresistance. It was reported that exosome-transmitted miRNA may promote chemosensitivity in multiple cancer types such as colorectal cancer and head and neck cancer (124,125), and recent studies have revealed that circRNAs mediate chemotherapy resistance in various types of cancer such as ovarian cancer and thyroid carcinoma (126)(127)(128). Hence, there is a novel hypothesis that exosomal circRNAs are influence chemotherapy resistance, but this still requires further experimental confirmation (Fig.…”

Integrated bioinformatics analysis of the association between apolipoprotein E expression and patient prognosis in papillary thyroid carcinoma

“…being mined. The majority of present studies are validated in animal tumor models, in vitro cell models or small-scale clinical studies (57,58). However, large-scale studies with more comprehensive analysis and larger cohorts are required due to the complexity of PTC.…”

Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

“…Therapy resistance may be attributed to autophagymediated changes in oxidative stress and autophagy-supplied key metabolites for the maintenance of stemness during dormancy [75][76][77][78]. Interestingly, circEIF6 promotes cisplatin-induced autophagy and enhances chemoresistance in GC cells [79].…”

“…Exposure of TPC1 and BHT101 cells to cisplatin further increases circEIF6 and decreases miR-144-3p expression. CircEIF6 upregulation promotes cisplatin-induced autophagy; thus, it enhances the resistance of PTC cells to cisplatin via the miR-144-3p/TGF-α axis [79].…”