LncRNA-IQCH-AS1 sensitizes thyroid cancer cells to doxorubicin via modulating the miR-196a-5p/PPP2R1B signalling pathway

Abstract

Thyroid cancer is a prevalent human endocrine tumour. Surgical resection is a primary approach for well-differentiated thyroid cancers. Currently, the combination of chemotherapy with subsequent irradiation is a therapeutic strategy for the late stage or metastatic thyroid cancer. Yet, drug resistance and side-effects greatly limit widely clinical applications of chemotherapeutic drugs. The long non-coding RNA IQCH antisense RNA 1 (IQCH-AS1) is correlated with survival and diagnosis of cancer patients. Currently, the precise roles of IQCH-AS1 in thyroid cancer and the chemosensitivity of doxorubicin remain unclear. Here, we report IQCH-AS1 was significantly down-regulated in thyroid cancer tissues and cell lines. Overexpression of IQCH-AS1 effectively sensitized thyroid cancer cells to doxorubicin. From the established doxorubicin-resistant thyroid cancer cell line, 8505 C Doxo R, we detected that IQCH-AS1 was remarkedly suppressed in doxorubicin-resistant cells. Bioinformatics analysis, RNA pull-down and luciferase assays illustrated that IQCH-AS1 functioned as a ceRNA of miR-196a-5p which showed an oncogenic role in thyroid cancer. Overexpression of miR-196a-5p, which was upregulated in 8505 C Doxo R cells, significantly de-sensitized thyroid cancer cells to doxorubicin. Furthermore, PPP2R1B, which encode the protein phosphatase 2 A regulatory subunit A, was directly targeted by miR-196a-5p in thyroid cancer cells. Rescue experiments validated that recovery of miR-196a-5p in IQCH-AS1-overexpressing 8508 C doxorubicin resistant cells successfully reversed the IQCH-AS1-promoted doxorubicin sensitization via targeting PPP2R1B. Summarily, our study revealed new functions and molecular targets of the lncRNA-IQCH-AS1-mediated chemosensitivity of thyroid cancer, contributing to the development of anti-chemoresistant strategies against thyroid cancer.