Yang Liu1, Peiru Yue2, Tao Zhou1, Fengzhen Zhang1, Huixiang Wang1, Xiaoqi Chen3. 1. Department of Nuclear Medicine, The First People's Hospital of Shangqiu, Shangqiu, 476000, China. 2. Department of Oncology, The First People's Hospital of Shangqiu, Shangqiu, 476000, China. 3. Department of Digestive Oncology, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, China. Electronic address: akkwedo@126.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: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.