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LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis
OBJECTIVE: Cisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). LncRNA noncoding RNA HLA complex group 11 (lncRNA HCG11) has been confirmed to promote GC progression. This study attempted to investigate the underlying molecular m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493275/ https://www.ncbi.nlm.nih.gov/pubmed/34629901 http://dx.doi.org/10.2147/CMAR.S329846 |
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author | Li, Yu Wang, Liqin Xu, Xiaoyi Sun, Heng Wu, Leilei |
author_facet | Li, Yu Wang, Liqin Xu, Xiaoyi Sun, Heng Wu, Leilei |
author_sort | Li, Yu |
collection | PubMed |
description | OBJECTIVE: Cisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). LncRNA noncoding RNA HLA complex group 11 (lncRNA HCG11) has been confirmed to promote GC progression. This study attempted to investigate the underlying molecular mechanism of HCG11 in DDP resistance of GC. METHODS: qRT-PCR was performed to evaluate the expression of HCG11, microRNA-144-3p (miR-144-3p), and ubiquitin-conjugating enzyme E2 D1 (UBE2D1) in GC. The correlation between HCG11 and clinicopathological features of GC patients was assessed. DDP-resistant GC cells and their parental cells were cultured in different concentrations of DDP. The role of HCG11 for the viability and the half maximal inhibitory concentration (IC50) of DDP in DDP-resistant GC cells was determined by MTT assay. Then, the invasion of DDP-resistant GC cells was measured by transwell assay. Next, a dual-luciferase reporter assay was used to confirm the interactions among HCG11, miR-144-3p, and UBE2D1 in GC. RESULTS: The expression of HCG11 and UBE2D1 was elevated in tumor tissues of GC patients, but miR-144-3p was declined. HCG11 expression was elevated in DDP-resistant GC patients and is strongly correlated with DDP sensitivity and World Health Organization grade in GC patients. HCG11 knockdown reduced the viability, IC50 of DDP, and invasion of DDP-resistant GC cells. Additionally, HCG11 targeted miR-144-3p and miR-144-3p further targeted UBE2D1. Feedback experiments indicated that low expression of miR-144-3p or overexpression of UBE2D1 mitigated the inhibitory effect of HCG11 depletion on DDP resistance of GC cells. CONCLUSION: HCG11 knockdown attenuated DDP resistance of GC cells through via miR-144-3p/UBE2D1 axis, affording a novel therapeutic strategy for GC. |
format | Online Article Text |
id | pubmed-8493275 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-84932752021-10-07 LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis Li, Yu Wang, Liqin Xu, Xiaoyi Sun, Heng Wu, Leilei Cancer Manag Res Original Research OBJECTIVE: Cisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). LncRNA noncoding RNA HLA complex group 11 (lncRNA HCG11) has been confirmed to promote GC progression. This study attempted to investigate the underlying molecular mechanism of HCG11 in DDP resistance of GC. METHODS: qRT-PCR was performed to evaluate the expression of HCG11, microRNA-144-3p (miR-144-3p), and ubiquitin-conjugating enzyme E2 D1 (UBE2D1) in GC. The correlation between HCG11 and clinicopathological features of GC patients was assessed. DDP-resistant GC cells and their parental cells were cultured in different concentrations of DDP. The role of HCG11 for the viability and the half maximal inhibitory concentration (IC50) of DDP in DDP-resistant GC cells was determined by MTT assay. Then, the invasion of DDP-resistant GC cells was measured by transwell assay. Next, a dual-luciferase reporter assay was used to confirm the interactions among HCG11, miR-144-3p, and UBE2D1 in GC. RESULTS: The expression of HCG11 and UBE2D1 was elevated in tumor tissues of GC patients, but miR-144-3p was declined. HCG11 expression was elevated in DDP-resistant GC patients and is strongly correlated with DDP sensitivity and World Health Organization grade in GC patients. HCG11 knockdown reduced the viability, IC50 of DDP, and invasion of DDP-resistant GC cells. Additionally, HCG11 targeted miR-144-3p and miR-144-3p further targeted UBE2D1. Feedback experiments indicated that low expression of miR-144-3p or overexpression of UBE2D1 mitigated the inhibitory effect of HCG11 depletion on DDP resistance of GC cells. CONCLUSION: HCG11 knockdown attenuated DDP resistance of GC cells through via miR-144-3p/UBE2D1 axis, affording a novel therapeutic strategy for GC. Dove 2021-10-01 /pmc/articles/PMC8493275/ /pubmed/34629901 http://dx.doi.org/10.2147/CMAR.S329846 Text en © 2021 Li et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Li, Yu Wang, Liqin Xu, Xiaoyi Sun, Heng Wu, Leilei LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis |
title | LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis |
title_full | LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis |
title_fullStr | LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis |
title_full_unstemmed | LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis |
title_short | LncRNA HLA Complex Group 11 Knockdown Alleviates Cisplatin Resistance in Gastric Cancer by Targeting the miR-144-3p/UBE2D1 Axis |
title_sort | lncrna hla complex group 11 knockdown alleviates cisplatin resistance in gastric cancer by targeting the mir-144-3p/ube2d1 axis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493275/ https://www.ncbi.nlm.nih.gov/pubmed/34629901 http://dx.doi.org/10.2147/CMAR.S329846 |
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