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Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1...

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Autores principales: Wu, Luyao, Ding, Yu, Tong, Houchao, Zhuang, Xi, Cai, Jingsheng, Si, Yan, Zhang, Hao, Wang, Xiaoting, Shen, Meiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296567/
https://www.ncbi.nlm.nih.gov/pubmed/34289835
http://dx.doi.org/10.1186/s12935-021-02097-2
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author Wu, Luyao
Ding, Yu
Tong, Houchao
Zhuang, Xi
Cai, Jingsheng
Si, Yan
Zhang, Hao
Wang, Xiaoting
Shen, Meiping
author_facet Wu, Luyao
Ding, Yu
Tong, Houchao
Zhuang, Xi
Cai, Jingsheng
Si, Yan
Zhang, Hao
Wang, Xiaoting
Shen, Meiping
author_sort Wu, Luyao
collection PubMed
description BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. METHODS: The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). RESULTS: Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. CONCLUSIONS: This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02097-2.
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spelling pubmed-82965672021-07-22 Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis Wu, Luyao Ding, Yu Tong, Houchao Zhuang, Xi Cai, Jingsheng Si, Yan Zhang, Hao Wang, Xiaoting Shen, Meiping Cancer Cell Int Primary Research BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. METHODS: The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). RESULTS: Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. CONCLUSIONS: This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-021-02097-2. BioMed Central 2021-07-21 /pmc/articles/PMC8296567/ /pubmed/34289835 http://dx.doi.org/10.1186/s12935-021-02097-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Wu, Luyao
Ding, Yu
Tong, Houchao
Zhuang, Xi
Cai, Jingsheng
Si, Yan
Zhang, Hao
Wang, Xiaoting
Shen, Meiping
Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis
title Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis
title_full Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis
title_fullStr Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis
title_full_unstemmed Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis
title_short Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis
title_sort long noncoding rna fer1l4 promotes the malignant processes of papillary thyroid cancer by targeting the mir-612/ cadherin 4 axis
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296567/
https://www.ncbi.nlm.nih.gov/pubmed/34289835
http://dx.doi.org/10.1186/s12935-021-02097-2
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