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N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression

BACKGROUND: Despite improvements in prognosis due to advances in treatment, including surgery, genetic screening, and molecular targeted therapy, the outcomes of ovarian cancer (OC) remain unsatisfactory. Internal mRNA modifications are extremely common in eukaryotes; N6-methyladenosine (m6A) altera...

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Autores principales: Gan, Lijuan, Zhao, Shengchao, Gao, Yang, Qi, Yuwen, Su, Min, Wang, Anjin, Cai, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561480/
https://www.ncbi.nlm.nih.gov/pubmed/37807062
http://dx.doi.org/10.1186/s13062-023-00420-7
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author Gan, Lijuan
Zhao, Shengchao
Gao, Yang
Qi, Yuwen
Su, Min
Wang, Anjin
Cai, Hongbing
author_facet Gan, Lijuan
Zhao, Shengchao
Gao, Yang
Qi, Yuwen
Su, Min
Wang, Anjin
Cai, Hongbing
author_sort Gan, Lijuan
collection PubMed
description BACKGROUND: Despite improvements in prognosis due to advances in treatment, including surgery, genetic screening, and molecular targeted therapy, the outcomes of ovarian cancer (OC) remain unsatisfactory. Internal mRNA modifications are extremely common in eukaryotes; N6-methyladenosine (m6A) alteration has significant effects on mRNA stability and translation, and it is involved in the pathophysiology of numerous diseases related to cancer. METHODS: Bioinformatics analysis, quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of vir-like m6A methyltransferase associated (KIAA1429) in OC tissues and cell lines. Several different cell models and animal models were established to determine the role of KIAA1429 in glucose metabolism reprogramming and the underlying molecular mechanism of OC. The mechanism of oncology functional assays, co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how KIAA1429 interacts with important molecular targets. RESULTS: We reported that KIAA1429 was overexpressed in OC and predicted a poor prognosis. Functionally, KIAA1429 promoted cell growth by inducing proliferation and inhibiting necrosis. Mechanistically, KIAA1429 promoted tumor progression and glycolysis via stabilizing ENO1 mRNA in a way dependent on m6A. Furthermore, we investigated that the SPI1 transcription factor is the main transcription factor that regulates KIAA1429 transcription in OC. CONCLUSION: Our findings revealed that SPI1/KIAA1429/ENO1 signaling is a novel molecular axis and raises awareness of the vital functions of the changes in KIAA1429 and m6A changes in the metabolic reprogramming of OC. These results identified new potential biomarkers and treatment targets for OC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00420-7.
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spelling pubmed-105614802023-10-10 N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression Gan, Lijuan Zhao, Shengchao Gao, Yang Qi, Yuwen Su, Min Wang, Anjin Cai, Hongbing Biol Direct Research BACKGROUND: Despite improvements in prognosis due to advances in treatment, including surgery, genetic screening, and molecular targeted therapy, the outcomes of ovarian cancer (OC) remain unsatisfactory. Internal mRNA modifications are extremely common in eukaryotes; N6-methyladenosine (m6A) alteration has significant effects on mRNA stability and translation, and it is involved in the pathophysiology of numerous diseases related to cancer. METHODS: Bioinformatics analysis, quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of vir-like m6A methyltransferase associated (KIAA1429) in OC tissues and cell lines. Several different cell models and animal models were established to determine the role of KIAA1429 in glucose metabolism reprogramming and the underlying molecular mechanism of OC. The mechanism of oncology functional assays, co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how KIAA1429 interacts with important molecular targets. RESULTS: We reported that KIAA1429 was overexpressed in OC and predicted a poor prognosis. Functionally, KIAA1429 promoted cell growth by inducing proliferation and inhibiting necrosis. Mechanistically, KIAA1429 promoted tumor progression and glycolysis via stabilizing ENO1 mRNA in a way dependent on m6A. Furthermore, we investigated that the SPI1 transcription factor is the main transcription factor that regulates KIAA1429 transcription in OC. CONCLUSION: Our findings revealed that SPI1/KIAA1429/ENO1 signaling is a novel molecular axis and raises awareness of the vital functions of the changes in KIAA1429 and m6A changes in the metabolic reprogramming of OC. These results identified new potential biomarkers and treatment targets for OC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00420-7. BioMed Central 2023-10-09 /pmc/articles/PMC10561480/ /pubmed/37807062 http://dx.doi.org/10.1186/s13062-023-00420-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 Research
Gan, Lijuan
Zhao, Shengchao
Gao, Yang
Qi, Yuwen
Su, Min
Wang, Anjin
Cai, Hongbing
N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression
title N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression
title_full N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression
title_fullStr N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression
title_full_unstemmed N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression
title_short N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression
title_sort n6-methyladenosine methyltransferase kiaa1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing eno1 expression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561480/
https://www.ncbi.nlm.nih.gov/pubmed/37807062
http://dx.doi.org/10.1186/s13062-023-00420-7
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