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Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer
Reprogrammed glucose metabolism of enhanced aerobic glycolysis, also known as Warburg effect, which exerts a significant contributor to cancer progression, is regarded as a hallmark of cancer. The roles of long noncoding RNAs (lncRNA) in regulating cancer via metabolic reprogramming are mostly unkno...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657677/ https://www.ncbi.nlm.nih.gov/pubmed/33204264 http://dx.doi.org/10.1155/2020/8847687 |
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author | Liu, Hai-E Shi, Hao-Hong Luo, Xing-Jing |
author_facet | Liu, Hai-E Shi, Hao-Hong Luo, Xing-Jing |
author_sort | Liu, Hai-E |
collection | PubMed |
description | Reprogrammed glucose metabolism of enhanced aerobic glycolysis, also known as Warburg effect, which exerts a significant contributor to cancer progression, is regarded as a hallmark of cancer. The roles of long noncoding RNAs (lncRNA) in regulating cancer via metabolic reprogramming are mostly unknown, including esophagal cancer (EC). Here, we showed that how the lncRNA urothelial carcinoma associated 1 (UCA1) exerts pro-oncogene in regulating EC glucose metabolism. Firstly, we found that upregulated UCA1 expression enhances the malignant phenotypes of EC, including poor outcome, larger tumor size, positive lymphatic invasion, and advanced pathological stages. UCA1 silencing could suppress EC cell proliferation and metastasis. Following, bioinformatics analyses revealed that UCA1 regulated the HK2 expression through functioning as a competing endogenous RNA (ceRNA). Mechanistically, UCA1 overexpression could elevate the activation of HK2 oncogenes via inhibition of miR-203 activity, as evidenced by the positive correlation of UCA1 with HK2 and inverse correlation with miR-203 expression. Luciferase activity assay further verified the targeting relationship between UCA1, miR-203, and HK2. Upregulated UCA1 in EC cells significantly suppressed the degradation of HK2 by miR-203. Further research showed that upregulated UCA1 effectively increased the rate of glucose uptake, lactate output, and ECAR value, all of which can be attenuate by HK2 interference and 2-DG, whereas knockdown of UCA1 had the opposite effect. In sum, our findings suggest that the UCA1/miR-203/HK2 axis contributes to EC development by reprogramming tumor glucose metabolism, providing new insight into the management of EC patients. |
format | Online Article Text |
id | pubmed-7657677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-76576772020-11-16 Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer Liu, Hai-E Shi, Hao-Hong Luo, Xing-Jing J Oncol Research Article Reprogrammed glucose metabolism of enhanced aerobic glycolysis, also known as Warburg effect, which exerts a significant contributor to cancer progression, is regarded as a hallmark of cancer. The roles of long noncoding RNAs (lncRNA) in regulating cancer via metabolic reprogramming are mostly unknown, including esophagal cancer (EC). Here, we showed that how the lncRNA urothelial carcinoma associated 1 (UCA1) exerts pro-oncogene in regulating EC glucose metabolism. Firstly, we found that upregulated UCA1 expression enhances the malignant phenotypes of EC, including poor outcome, larger tumor size, positive lymphatic invasion, and advanced pathological stages. UCA1 silencing could suppress EC cell proliferation and metastasis. Following, bioinformatics analyses revealed that UCA1 regulated the HK2 expression through functioning as a competing endogenous RNA (ceRNA). Mechanistically, UCA1 overexpression could elevate the activation of HK2 oncogenes via inhibition of miR-203 activity, as evidenced by the positive correlation of UCA1 with HK2 and inverse correlation with miR-203 expression. Luciferase activity assay further verified the targeting relationship between UCA1, miR-203, and HK2. Upregulated UCA1 in EC cells significantly suppressed the degradation of HK2 by miR-203. Further research showed that upregulated UCA1 effectively increased the rate of glucose uptake, lactate output, and ECAR value, all of which can be attenuate by HK2 interference and 2-DG, whereas knockdown of UCA1 had the opposite effect. In sum, our findings suggest that the UCA1/miR-203/HK2 axis contributes to EC development by reprogramming tumor glucose metabolism, providing new insight into the management of EC patients. Hindawi 2020-11-04 /pmc/articles/PMC7657677/ /pubmed/33204264 http://dx.doi.org/10.1155/2020/8847687 Text en Copyright © 2020 Hai-E Liu et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Liu, Hai-E Shi, Hao-Hong Luo, Xing-Jing Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer |
title | Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer |
title_full | Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer |
title_fullStr | Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer |
title_full_unstemmed | Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer |
title_short | Upregulated Long Noncoding RNA UCA1 Enhances Warburg Effect via miR-203/HK2 Axis in Esophagal Cancer |
title_sort | upregulated long noncoding rna uca1 enhances warburg effect via mir-203/hk2 axis in esophagal cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657677/ https://www.ncbi.nlm.nih.gov/pubmed/33204264 http://dx.doi.org/10.1155/2020/8847687 |
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