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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2021

Open Access 01-12-2021 | Metastasis | Research

circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling

Authors: Xun Zheng, Shu Rui, Xiao-Fei Wang, Xiu-He Zou, Yan-Ping Gong, Zhi-Hui Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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Abstract

Background

Medullary thyroid cancer (MTC) represents 13.4 % of all thyroid cancers-related deaths. The treatments for MTC are very limited especially for patients with distal metastasis. Therefore, it is critical to understand the mechanisms of MTC to pursue novel therapeutic avenues. Here, we studied the function of circPVT1/miR-455-5p in MTC.

Methods

Human MTC tissues and cell lines were used. qRT-PCR and Western blotting were employed to measure expression levels of miR-455-5p, circPVT1, CXCL12, and epithelial mesenchymal transformation (EMT)-related proteins. Colony formation assay, flow cytometry, transwell assay, and scratch wound healing assay were used to assess the abilities of cell proliferation, apoptosis, migration and invasion, respectively. Dual luciferase assay and RNA immunoprecipitation were employed to validate interactions of circPVT1/miR-455-5p and miR-455-5p/CXCL12. Nude mouse xenograft model was used to evaluate the effects of shcircPVT1 and miR-455-5p mimics on tumor growth and metastasis in vivo.

Results

miR-455-5p was reduced in MTC tissues and cells while circPVT1 was elevated. Their levels were correlated with prognosis of MTC. Overexpression of miR-455-5p or sh-circPVT1 suppressed EMT and MTC cell proliferation, migration and invasion. miR-455-5p targeted CXCL12 while circPVT1 sponged miR-455-5p. Knockdown of CXCL12 or CXCL12/CXCR4 signaling inhibitor reversed the effects of circPVT1 overexpression or miR-455-5p inhibitor on EMT and MTC cell proliferation, migration and invasion. Knockdown of circPVT1 or miR-455-5p overexpression repressed MTC tumor growth and lung metastasis in vivo.

Conclusions

miR-455-5p suppresses MTC growth and metastasis by targeting CXCL12/CXCR4 signaling pathway while circPVT1 promotes MTC by sponging miR-455-5p. Our study sheds light on the mechanisms of MTC growth and metastasis.
Appendix
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Metadata
Title
circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling
Authors
Xun Zheng
Shu Rui
Xiao-Fei Wang
Xiu-He Zou
Yan-Ping Gong
Zhi-Hui Li
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-021-01964-0

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