The flow chart schematic model. ¹³¹I-resistant TC cells induce down-regulation of MEG3. Then, decreased MEG3 resulted in an increase of miR-182 expression. Finally, up-regulated miR-182 enhanced ¹³¹I resistance of TC cells by facilitating proliferation, as well as suppressing apoptosis and DNA damage.

Long non-coding RNA (LncRNA) MEG3 has been demonstrated as a tumor suppressor in various cancers, including thyroid carcinoma (TC). However, the detail functions and possible mechanisms of MEG3 in ¹³¹I resistance of TC remain to be uncovered.

qRT-PCR was performed for the detection of MEG3 and miR-182 levels. ¹³¹I-resistant TC cells were constructed by continuous exposure to stepwise increased concentrations of ¹³¹I. Western blot assay was used to measure the protein expressions of γ-H2 AX and H2 AX. CCK-8 and flow cytometry assays were carried out for the evaluation of cell viability and apoptosis, respectively. Bioinformatics and dual-luciferse assays were conducted to prove the interaction of MEG3 and miR-182.

MEG3 expression was down-regulated in TC tumor tissues, and the cumulative survival rate was decreased in low MEG3 expression group in TC patients under ¹³¹I treatment. MEG3 expression appeared a decline and miR-182 expression displayed an increase in ¹³¹I-resistant FTC-133 (res-FTC-133) and TPC-1 (res-TPC-1) cells. Moreover, MEG3 overexpression suppressed ¹³¹I-resistant cell viability, promoted apoptosis and induced DNA damage. MEG3 was verified as a molecular sponge for miR-182, and inhibition of miR-182 exerted similar functions as MEG3 overexpression. Furthermore, MEG3 knockdown substantially abrogated the anti-cancer functions of anti-miR-182.

MEG3 enhanced the radiosensitivity of ¹³¹I in TC cells via sponging miR-182, indicating that MEG3 may act as a potential biomarker and therapeutic target for TC patients with ¹³¹I resistance.