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The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression
BACKGROUND: Long non-coding RNAs (lncRNAs) play critical roles in gastric cancer (GC) initiation progression. However, the biological function of the lncRNA telomerase RNA component (TERC) remains unknown in human GC. The present study sought to determine the biological function and underlying molec...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577797/ https://www.ncbi.nlm.nih.gov/pubmed/36267723 http://dx.doi.org/10.21037/atm-22-3545 |
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author | Wang, Jianhua Wu, Min Chang, Le Jin, Zhankui Yang, Xiaoli Li, Dongliang Wang, Jiaojiao Qu, Jie Hou, Qiang Huang, Xiaoyan Xu, Cuixiang |
author_facet | Wang, Jianhua Wu, Min Chang, Le Jin, Zhankui Yang, Xiaoli Li, Dongliang Wang, Jiaojiao Qu, Jie Hou, Qiang Huang, Xiaoyan Xu, Cuixiang |
author_sort | Wang, Jianhua |
collection | PubMed |
description | BACKGROUND: Long non-coding RNAs (lncRNAs) play critical roles in gastric cancer (GC) initiation progression. However, the biological function of the lncRNA telomerase RNA component (TERC) remains unknown in human GC. The present study sought to determine the biological function and underlying molecular mechanism of the lncRNA TERC in GC progression. METHODS: The expression levels of the lncRNA TERC in GC tissues and cell lines were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of the lncRNA TERC on the proliferation, migration, and invasion of GC cells were determined using Cell Counting Kit-8 (CCK-8) and Transwell assays. Dual luciferase reporter and argonaute 2 (AGO2)-RNA immunoprecipitation (RIP) assays were used to detect the binding between the lncRNA TERC and microRNA-423-5p (miR-423-5p). Western blotting was performed to measure the expression levels of sex determining region Y-box 12 (SOX12), N-cadherin, E-cadherin, matrix metallopeptidase 9 (MMP9), and proliferating cell nuclear antigen (PCNA). RESULTS: The results demonstrated that the lncRNA TERC expression levels were upregulated in GC cells and tissues, while miR-423-5p expression levels were downregulated. The upregulation of the lncRNA TERC was associated with a shorter overall survival in patients with GC. The knockdown of the lncRNA TERC significantly reduced the proliferation, migration, and invasion of human GC cell lines HGC-27 and SNU-1 cells. Further, the lncRNA TERC knockdown in the HGC-27 and SNU-1 cells significantly downregulated the expression levels of SOX12, N-cadherin, MMP9, and PCNA, and upregulated the expression levels of miR-423-5p and E-cadherin. MiR-423-5p was also identified as a target of the lncRNA TERC and was found to directly bind to the lncRNA TERC. Additionally, miR-423-5p was found to directly target SOX12 to inhibit the proliferation, migration, and invasion of the HGC-27 and SNU-1 cells. CONCLUSIONS: In conclusion, the findings of this study suggested that the lncRNA TERC may regulate the miR-423-5p/SOX12 signaling axis by directly sponging miR-423-5p and inhibiting SOX12 expression, thereby leading to the progression of GC. These findings may reveal novel targets for future GC therapy. |
format | Online Article Text |
id | pubmed-9577797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-95777972022-10-19 The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression Wang, Jianhua Wu, Min Chang, Le Jin, Zhankui Yang, Xiaoli Li, Dongliang Wang, Jiaojiao Qu, Jie Hou, Qiang Huang, Xiaoyan Xu, Cuixiang Ann Transl Med Original Article BACKGROUND: Long non-coding RNAs (lncRNAs) play critical roles in gastric cancer (GC) initiation progression. However, the biological function of the lncRNA telomerase RNA component (TERC) remains unknown in human GC. The present study sought to determine the biological function and underlying molecular mechanism of the lncRNA TERC in GC progression. METHODS: The expression levels of the lncRNA TERC in GC tissues and cell lines were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of the lncRNA TERC on the proliferation, migration, and invasion of GC cells were determined using Cell Counting Kit-8 (CCK-8) and Transwell assays. Dual luciferase reporter and argonaute 2 (AGO2)-RNA immunoprecipitation (RIP) assays were used to detect the binding between the lncRNA TERC and microRNA-423-5p (miR-423-5p). Western blotting was performed to measure the expression levels of sex determining region Y-box 12 (SOX12), N-cadherin, E-cadherin, matrix metallopeptidase 9 (MMP9), and proliferating cell nuclear antigen (PCNA). RESULTS: The results demonstrated that the lncRNA TERC expression levels were upregulated in GC cells and tissues, while miR-423-5p expression levels were downregulated. The upregulation of the lncRNA TERC was associated with a shorter overall survival in patients with GC. The knockdown of the lncRNA TERC significantly reduced the proliferation, migration, and invasion of human GC cell lines HGC-27 and SNU-1 cells. Further, the lncRNA TERC knockdown in the HGC-27 and SNU-1 cells significantly downregulated the expression levels of SOX12, N-cadherin, MMP9, and PCNA, and upregulated the expression levels of miR-423-5p and E-cadherin. MiR-423-5p was also identified as a target of the lncRNA TERC and was found to directly bind to the lncRNA TERC. Additionally, miR-423-5p was found to directly target SOX12 to inhibit the proliferation, migration, and invasion of the HGC-27 and SNU-1 cells. CONCLUSIONS: In conclusion, the findings of this study suggested that the lncRNA TERC may regulate the miR-423-5p/SOX12 signaling axis by directly sponging miR-423-5p and inhibiting SOX12 expression, thereby leading to the progression of GC. These findings may reveal novel targets for future GC therapy. AME Publishing Company 2022-09 /pmc/articles/PMC9577797/ /pubmed/36267723 http://dx.doi.org/10.21037/atm-22-3545 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Wang, Jianhua Wu, Min Chang, Le Jin, Zhankui Yang, Xiaoli Li, Dongliang Wang, Jiaojiao Qu, Jie Hou, Qiang Huang, Xiaoyan Xu, Cuixiang The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression |
title | The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression |
title_full | The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression |
title_fullStr | The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression |
title_full_unstemmed | The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression |
title_short | The lncRNA TERC promotes gastric cancer cell proliferation, migration, and invasion by sponging miR-423-5p to regulate SOX12 expression |
title_sort | lncrna terc promotes gastric cancer cell proliferation, migration, and invasion by sponging mir-423-5p to regulate sox12 expression |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577797/ https://www.ncbi.nlm.nih.gov/pubmed/36267723 http://dx.doi.org/10.21037/atm-22-3545 |
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