hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4

We identified a novel interactome, circ_0001018/miR-338-3p/SOX4, in papillary thyroid cancer (PTC), and we intended to confirm the regulatory relationship between the three and to study the effects of the three in PTC. The bioinformatics method was used to screen out the circular RNA and mRNA of int...

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Main Authors: Qiang Luo, Feng Guo, Qingfeng Fu, Guoqing Sui
Format: Article
Language:English
Published: Elsevier 2021-06-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253121000585
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author Qiang Luo
Feng Guo
Qingfeng Fu
Guoqing Sui
author_facet Qiang Luo
Feng Guo
Qingfeng Fu
Guoqing Sui
author_sort Qiang Luo
collection DOAJ
description We identified a novel interactome, circ_0001018/miR-338-3p/SOX4, in papillary thyroid cancer (PTC), and we intended to confirm the regulatory relationship between the three and to study the effects of the three in PTC. The bioinformatics method was used to screen out the circular RNA and mRNA of interest. A cellular fractionation assay and fluorescence in situ hybridization (FISH) assay were conducted to prove that circ_0001018 and CCT4 (the host gene of circ_0001018) mRNA primarily localized in the cytoplasm of PTC cell lines. By qRT-PCR analysis, the expression of circ_0001018 and SOX4 mRNA was found upregulated while the expression of miR-338-3p was found downregulated in PTC tissues and cells. circ_0001018 silence significantly inhibited the tumor growth in xenografted nude mice. A series of cytological experiments such as a Cell Counting Kit-8 (CCK-8) assay, a 5-ethynyl-2′-deoxyuridine (EdU) assay, cell cycle profiling, wound healing, a transwell assay, and cell apoptosis were conducted and showed that circ_0001018 and SOX4 promoted cell proliferation, migration, and invasion, inhibited cell apoptosis, and reduced the cell cycle arrest at the G1 phase in PTC cells. Compared with circ_0001018 and SOX4, miR-338-3p held the opposite function. The regulatory relationship between circ_0001018 and miR-338-3p, and between miR-338-3p and SOX4 mRNA, was validated using a luciferase reporter gene assay and/or RNA immunoprecipitation (RIP assay). Our findings showed that circ_0001018 acted as the tumor promoter via sponging miR-338-3p to elevate SOX4 expression level in PTC. Importantly, this novel circ_0001018/miR-338-3p/SOX4 axis has the potential to be considered as a therapy target for PTC.
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spelling doaj.art-4237ddee6e324ef28ba04e3e385f17ef2022-12-21T20:04:27ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-06-0124591609hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4Qiang Luo0Feng Guo1Qingfeng Fu2Guoqing Sui3Department of Ultrasound, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, ChinaDepartment of Ultrasound, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, ChinaJilin Provincial Key Laboratory of Surgical Translational Medicine, Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, ChinaDepartment of Ultrasound, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, China; Corresponding author: Guoqing Sui, Department of Ultrasound, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, China.We identified a novel interactome, circ_0001018/miR-338-3p/SOX4, in papillary thyroid cancer (PTC), and we intended to confirm the regulatory relationship between the three and to study the effects of the three in PTC. The bioinformatics method was used to screen out the circular RNA and mRNA of interest. A cellular fractionation assay and fluorescence in situ hybridization (FISH) assay were conducted to prove that circ_0001018 and CCT4 (the host gene of circ_0001018) mRNA primarily localized in the cytoplasm of PTC cell lines. By qRT-PCR analysis, the expression of circ_0001018 and SOX4 mRNA was found upregulated while the expression of miR-338-3p was found downregulated in PTC tissues and cells. circ_0001018 silence significantly inhibited the tumor growth in xenografted nude mice. A series of cytological experiments such as a Cell Counting Kit-8 (CCK-8) assay, a 5-ethynyl-2′-deoxyuridine (EdU) assay, cell cycle profiling, wound healing, a transwell assay, and cell apoptosis were conducted and showed that circ_0001018 and SOX4 promoted cell proliferation, migration, and invasion, inhibited cell apoptosis, and reduced the cell cycle arrest at the G1 phase in PTC cells. Compared with circ_0001018 and SOX4, miR-338-3p held the opposite function. The regulatory relationship between circ_0001018 and miR-338-3p, and between miR-338-3p and SOX4 mRNA, was validated using a luciferase reporter gene assay and/or RNA immunoprecipitation (RIP assay). Our findings showed that circ_0001018 acted as the tumor promoter via sponging miR-338-3p to elevate SOX4 expression level in PTC. Importantly, this novel circ_0001018/miR-338-3p/SOX4 axis has the potential to be considered as a therapy target for PTC.http://www.sciencedirect.com/science/article/pii/S2162253121000585circ_0001018miR-338-3pSOX4papillary thyroid carcinoma
spellingShingle Qiang Luo
Feng Guo
Qingfeng Fu
Guoqing Sui
hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4
Molecular Therapy: Nucleic Acids
circ_0001018
miR-338-3p
SOX4
papillary thyroid carcinoma
title hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4
title_full hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4
title_fullStr hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4
title_full_unstemmed hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4
title_short hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4
title_sort hsa circ 0001018 promotes papillary thyroid cancer by facilitating cell survival invasion g1 s cell cycle progression and repressing cell apoptosis via crosstalk with mir 338 3p and sox4
topic circ_0001018
miR-338-3p
SOX4
papillary thyroid carcinoma
url http://www.sciencedirect.com/science/article/pii/S2162253121000585
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