Dataset Information

LncRNA CASC2 Enhances ¹³¹I Sensitivity in Papillary Thyroid Cancer by Sponging miR-155.

ABSTRACT: Long noncoding RNA cancer susceptibility candidate 2 (CASC2) has been reported to play an anticancer role in papillary thyroid cancer (PTC). Radioiodine (¹³¹I) is a common option for the treatment of PTC. However, the role and mechanism of CASC2 in ¹³¹I sensitivity remain unclear. In this study, ¹³¹I-resistant cells were constructed through continuous treatment of ¹³¹I. The expression levels of CASC2 and miR-155 were measured by qRT-PCR. The IC50 of ¹³¹I was analyzed by cell viability using MTT assay. Flow cytometry was conducted to determine cell apoptosis induced by ¹³¹I. The association between CASC2 and miR-155 was evaluated by luciferase assay and RNA immunoprecipitation. A mouse xenograft model was built to explore the effect of CASC2 on the growth of ¹³¹I-resistant PTC cells in vivo. Results showed that CASC2 expression was decreased in PTC tissues and cells, and low expression of CASC2 was associated with poor outcome of patients. CASC2 level was reduced in ¹³¹I-resistant cells. Knockdown of CASC2 inhibited ¹³¹I sensitivity in thyroid cancer cells. Overexpression of CASC2 enhanced ¹³¹I sensitivity in constructed resistant PTC cells. CASC2 was a decoy of miR-155, and CASC2-mediated promotion of ¹³¹I sensitivity was weakened by decreasing miR-155. Abundance of CASC2 inhibited the growth of ¹³¹I-resistant cells in vivo. As a conclusion, CASC2 increases ¹³¹I sensitivity in PTC by sponging miR-155, providing a novel target for the treatment of thyroid cancer patients with ¹³¹I resistance.

SUBMITTER: Tao L

PROVIDER: S-EPMC7591961 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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lncRNA CASC2 Enhances 131I Sensitivity in Papillary Thyroid Cancer by Sponging miR-155.

Tao Ling L Tian Ping P Yang Li L Guo Xiangyang X

BioMed research international 20201019

Long noncoding RNA cancer susceptibility candidate 2 (CASC2) has been reported to play an anticancer role in papillary thyroid cancer (PTC). Radioiodine (131I) is a common option for the treatment of PTC. However, the role and mechanism of CASC2 in 131I sensitivity remain unclear. In this study, 131I-resistant cells were constructed through continuous treatment of 131I. The expression levels of CASC2 and miR-155 were measured by qRT-PCR. The IC50 of <s ...[more]

PMID: 33134385

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Project description:Patients with metastatic differentiated thyroid cancer (DTC) may be prepared using either thyroid-stimulating hormone withdrawal (THW) or recombinant human thyroid-stimulating hormone (rhTSH) injections before 131I administration for treatment. The objective of this study was to compare the absorbed dose to the critical organs and tumors determined by 124I PET/CT-based dosimetry for 131I therapy of metastatic DTC when the same patient was prepared with and imaged after both THW and rhTSH injections. Methods: Four DTC patients at MedStar Washington Hospital Center were first prepared using the rhTSH method and imaged by 124I PET/CT at 2, 24, 48, 72, and 96 h after administration of approximately 30-63 MBq of 124I. After 5-8 wk, the same patients were prepared using the THW method and imaged as before. The 124I PET/CT images acquired as part of a prospective study were used to perform retrospective dosimetric calculations for 131I therapy for the normal organs with the dosimetry package 3D-RD. The absorbed doses from 131I for the lungs, liver, heart, kidneys, and bone marrow were obtained for each study (rhTSH and THW). Twenty-two lesions in 3 patients were identified. The contours were drawn on each PET image of each study. Time-integrated activity coefficients were calculated and used as input in OLINDA/EXM sphere dose calculator to obtain the absorbed dose to tumors. Results: The THW-to-rhTSH organ absorbed dose ratio averaged over 5 organs for the first 3 patients was 1.5, 2.5, and 0.64, respectively, and averaged over 3 organs for the fourth patient was 1.1. The absorbed dose per unit administered activity to the bone marrow was 0.13, 0.086, 0.33, and 0.068 mGy/MBq after rhTSH and 0.11, 0.14, 0.22, and 0.080 mGy/MBq after THW for each patient, respectively. With the exception of 3 lesions of 1 patient, the absorbed dose per unit administered activity of 131I was higher in the THW study than in the rhTSH study. The ratio of the average tumor absorbed dose after stimulation by THW compared with stimulation by rhTSH injections was 3.9, 27, and 1.4 for patient 1, patient 2, and patient 3, respectively. The ratio of mean tumor to bone marrow absorbed dose per unit administered activity of 131I, after THW and rhTSH, was 232 and 62 (patient 1), 12 and 0.78 (patient 2), and 22 and 11 (patient 3), respectively. Conclusion: The results suggest a high patient variability in the overall absorbed dose to the normal organs per MBq of 131I administered, between the 2 TSH stimulation methods. The tumor-to-dose-limiting-organ (bone marrow) absorbed dose ratio, that is, the therapeutic index, was higher in the THW-aided than rhTSH-aided administrations. Additional comparison for tumor and normal organ absorbed dose in patients prepared using both methods is needed before definitive conclusions may be drawn regarding rhTSH versus THW patient preparation methods for 131I therapy of metastatic DTC.

Dataset Information

LncRNA CASC2 Enhances ¹³¹I Sensitivity in Papillary Thyroid Cancer by Sponging miR-155.

Publications

lncRNA CASC2 Enhances <sup>131</sup>I Sensitivity in Papillary Thyroid Cancer by Sponging miR-155.

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Dataset Information

LncRNA CASC2 Enhances 131I Sensitivity in Papillary Thyroid Cancer by Sponging miR-155.

Publications

lncRNA CASC2 Enhances <sup>131</sup>I Sensitivity in Papillary Thyroid Cancer by Sponging miR-155.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

LncRNA CASC2 Enhances ¹³¹I Sensitivity in Papillary Thyroid Cancer by Sponging miR-155.