TBX3 activating PVT1 accelerates proliferation, migration, and invasion by modulating the miR-30a/LOX axis in anaplastic thyroid carcinoma

ENDOKRYNOLOGIA POLSKA(2022)

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Abstract
Introduction: Anaplastic thyroid carcinoma (ATC) is a nearly chemo-resistant malignancy with high invasion and mortality. Long non-coding RNAs (lncRNAs) have been demonstrated to be dysregulated and play a crucial role in the development and process of ATC. The present study aimed to explore the mechanism of PVT1 dysregulation in ATC.Material and methods: The mRNA levels of PVT1 and T-box3 (TBX3), and the protein levels of TBX3 in ATC and paracancerous tissues, and FRO and Nthy-ori 3-1 cells were determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and west-ern blot, respectively. The transcriptional factor binding site was predicted and validated between TBX3 and PVT1 promoter through the JASPAR website, and ChIP and luciferase analysis. The proliferation, migration, and invasion of FRO cells were assessed by MTT, colony formation, and transwell assays.Results: PVT1 expression was upregulated in ATC, which was positively correlative with the level of transcription factor TBX3. Downregu-lation of PVT1 inhibited the proliferation, migration, and invasion of FRO cells. Moreover, TBX3 targeting the promoter region of PVT1 promoted the expression level of PVT1 and modulated the downstream signalling axis of PVT1, miR-30a/LOX. Also, interference of PVT1 reversed the stimulative role of overexpression of TBX3 in the progress of FRO cells.Conclusion: TBX3 enhanced proliferation, migration, and invasion of ATC cells via activation of PVT1 and modulation of the miR-30a/LOX signalling axis. (Endokrynol Pol 2022; 73 (4): 690-698)
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Key words
anaplastic thyroid carcinoma, PVT1, TBX3, proliferation, migration, invasion
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