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LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy

AIM: Long noncoding RNAs (lncRNAs) are key mediators with a wide range of pathophysiological functions, but their role in human hepatocellular carcinoma (HCC) is still unclear. METHODS: An unbiased microarray study evaluated a novel lncRNA, HClnc1, that is linked to the development of HCC. In vitro...

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Autores principales: Zhu, Qian, Lei, Zhengqing, Xu, Chang, Zhang, Zheng, Yu, Zeqian, Cheng, Zhangjun, Xiao, Pengfeng, Li, Shufeng, Yu, Weiping, Zhou, Jiahua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10358232/
https://www.ncbi.nlm.nih.gov/pubmed/37212467
http://dx.doi.org/10.1002/cam4.6117
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author Zhu, Qian
Lei, Zhengqing
Xu, Chang
Zhang, Zheng
Yu, Zeqian
Cheng, Zhangjun
Xiao, Pengfeng
Li, Shufeng
Yu, Weiping
Zhou, Jiahua
author_facet Zhu, Qian
Lei, Zhengqing
Xu, Chang
Zhang, Zheng
Yu, Zeqian
Cheng, Zhangjun
Xiao, Pengfeng
Li, Shufeng
Yu, Weiping
Zhou, Jiahua
author_sort Zhu, Qian
collection PubMed
description AIM: Long noncoding RNAs (lncRNAs) are key mediators with a wide range of pathophysiological functions, but their role in human hepatocellular carcinoma (HCC) is still unclear. METHODS: An unbiased microarray study evaluated a novel lncRNA, HClnc1, that is linked to the development of HCC. In vitro cell proliferation assays and an in vivo xenotransplanted HCC tumor model were performed to determine its functions, followed by antisense oligo‐coupled mass spectrometry to identify HClnc1‐interacting proteins. To study relevant signaling pathways, in vitro experiments were performed, including chromatin isolation by RNA purification, RNA immunoprecipitation, luciferase, and RNA pull‐down assay. RESULTS: HClnc1 levels were considerably greater in patients with advanced tumor‐node‐metastatic stages, and it was found to be inversely connected to survival rates. Moreover, the proliferative and invasive potential of the HCC cells was attenuated by HClnc1 RNA knockdown in vitro, while HCC tumor growth and metastasis were found to be reduced in vivo. HClnc1 interacted with pyruvate kinase M2 (PKM2) to prevent its degradation and thus facilitated aerobic glycolysis and PKM2‐STAT3 signaling. CONCLUSIONS: HClnc1 is involved in a novel epigenetic mechanism of HCC tumorigenesis and PKM2 regulation. HClnc1 is not only a more accurate prognostic indicator of HCC but also a potential therapeutic target for HCC treatment.
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spelling pubmed-103582322023-07-21 LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy Zhu, Qian Lei, Zhengqing Xu, Chang Zhang, Zheng Yu, Zeqian Cheng, Zhangjun Xiao, Pengfeng Li, Shufeng Yu, Weiping Zhou, Jiahua Cancer Med RESEARCH ARTICLES AIM: Long noncoding RNAs (lncRNAs) are key mediators with a wide range of pathophysiological functions, but their role in human hepatocellular carcinoma (HCC) is still unclear. METHODS: An unbiased microarray study evaluated a novel lncRNA, HClnc1, that is linked to the development of HCC. In vitro cell proliferation assays and an in vivo xenotransplanted HCC tumor model were performed to determine its functions, followed by antisense oligo‐coupled mass spectrometry to identify HClnc1‐interacting proteins. To study relevant signaling pathways, in vitro experiments were performed, including chromatin isolation by RNA purification, RNA immunoprecipitation, luciferase, and RNA pull‐down assay. RESULTS: HClnc1 levels were considerably greater in patients with advanced tumor‐node‐metastatic stages, and it was found to be inversely connected to survival rates. Moreover, the proliferative and invasive potential of the HCC cells was attenuated by HClnc1 RNA knockdown in vitro, while HCC tumor growth and metastasis were found to be reduced in vivo. HClnc1 interacted with pyruvate kinase M2 (PKM2) to prevent its degradation and thus facilitated aerobic glycolysis and PKM2‐STAT3 signaling. CONCLUSIONS: HClnc1 is involved in a novel epigenetic mechanism of HCC tumorigenesis and PKM2 regulation. HClnc1 is not only a more accurate prognostic indicator of HCC but also a potential therapeutic target for HCC treatment. John Wiley and Sons Inc. 2023-05-22 /pmc/articles/PMC10358232/ /pubmed/37212467 http://dx.doi.org/10.1002/cam4.6117 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle RESEARCH ARTICLES
Zhu, Qian
Lei, Zhengqing
Xu, Chang
Zhang, Zheng
Yu, Zeqian
Cheng, Zhangjun
Xiao, Pengfeng
Li, Shufeng
Yu, Weiping
Zhou, Jiahua
LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy
title LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy
title_full LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy
title_fullStr LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy
title_full_unstemmed LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy
title_short LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy
title_sort lncrna hclnc1 facilitates hepatocellular carcinoma progression by regulating pkm2 signaling and indicates poor survival outcome after hepatectomy
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10358232/
https://www.ncbi.nlm.nih.gov/pubmed/37212467
http://dx.doi.org/10.1002/cam4.6117
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