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Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p

Betulinic acid (BA) is a natural product extracted from a broad range of medicinal and edible herbal plants. Previous studies showed that BA induces cell death in tumors derived from multiple tissues; however, the underlying mechanism remains obscure. The present study aimed to study the effects of...

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Autores principales: Chen, Feiyu, Zhong, Zhangfeng, Tan, Hor Yue, Guo, Wei, Zhang, Cheng, Cheng, Chien‐Shan, Wang, Ning, Ren, Junguo, Feng, Yibin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586994/
https://www.ncbi.nlm.nih.gov/pubmed/33135336
http://dx.doi.org/10.1002/ctm2.190
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author Chen, Feiyu
Zhong, Zhangfeng
Tan, Hor Yue
Guo, Wei
Zhang, Cheng
Cheng, Chien‐Shan
Wang, Ning
Ren, Junguo
Feng, Yibin
author_facet Chen, Feiyu
Zhong, Zhangfeng
Tan, Hor Yue
Guo, Wei
Zhang, Cheng
Cheng, Chien‐Shan
Wang, Ning
Ren, Junguo
Feng, Yibin
author_sort Chen, Feiyu
collection PubMed
description Betulinic acid (BA) is a natural product extracted from a broad range of medicinal and edible herbal plants. Previous studies showed that BA induces cell death in tumors derived from multiple tissues; however, the underlying mechanism remains obscure. The present study aimed to study the effects of BA on autophagy and apoptosis of hepatocellular carcinoma (HCC). Human HCC cell lines and orthotopic HCC implanted mice were employed to examine the BA‐induced tumor suppression; RT(2) long noncoding RNA (lncRNA) PCR array and database analysis were used to explore the possible mechanisms; validation of pathways was performed using siRNA and miRNA inhibitors. The results indicated that BA regulated autophagy and induced apoptosis in HCC. The degradation of inhibitor of apoptosis proteins (IAPs), the conversion of LC3‐I to LC3‐II, and p62 accumulation were enhanced by BA, thereby suggesting that the downregulation of IAPs and autophagic cell death are induced by BA. The addition of autophagy and lysosomal inhibitors indicated that BA induced autophagy‐independent apoptosis via degradation of IAPs. Moreover, RT(2) lncRNA PCR array and database analysis suggested that BA downregulated the levels of lncRNA MALAT1, which is considered to be an oncogene. Further investigations demonstrated that lncRNA MALAT1 functioned as a ceRNA (competing endogenous RNA) to contribute to BA‐mediated degradation of IAPs by sponging miR‐22‐3p. Therefore, BA could be developed as a potential anticancer agent for HCC.
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spelling pubmed-75869942020-10-30 Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p Chen, Feiyu Zhong, Zhangfeng Tan, Hor Yue Guo, Wei Zhang, Cheng Cheng, Chien‐Shan Wang, Ning Ren, Junguo Feng, Yibin Clin Transl Med Research Articles Betulinic acid (BA) is a natural product extracted from a broad range of medicinal and edible herbal plants. Previous studies showed that BA induces cell death in tumors derived from multiple tissues; however, the underlying mechanism remains obscure. The present study aimed to study the effects of BA on autophagy and apoptosis of hepatocellular carcinoma (HCC). Human HCC cell lines and orthotopic HCC implanted mice were employed to examine the BA‐induced tumor suppression; RT(2) long noncoding RNA (lncRNA) PCR array and database analysis were used to explore the possible mechanisms; validation of pathways was performed using siRNA and miRNA inhibitors. The results indicated that BA regulated autophagy and induced apoptosis in HCC. The degradation of inhibitor of apoptosis proteins (IAPs), the conversion of LC3‐I to LC3‐II, and p62 accumulation were enhanced by BA, thereby suggesting that the downregulation of IAPs and autophagic cell death are induced by BA. The addition of autophagy and lysosomal inhibitors indicated that BA induced autophagy‐independent apoptosis via degradation of IAPs. Moreover, RT(2) lncRNA PCR array and database analysis suggested that BA downregulated the levels of lncRNA MALAT1, which is considered to be an oncogene. Further investigations demonstrated that lncRNA MALAT1 functioned as a ceRNA (competing endogenous RNA) to contribute to BA‐mediated degradation of IAPs by sponging miR‐22‐3p. Therefore, BA could be developed as a potential anticancer agent for HCC. John Wiley and Sons Inc. 2020-10-14 /pmc/articles/PMC7586994/ /pubmed/33135336 http://dx.doi.org/10.1002/ctm2.190 Text en © 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics This is an open access article under the terms of the http://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
Chen, Feiyu
Zhong, Zhangfeng
Tan, Hor Yue
Guo, Wei
Zhang, Cheng
Cheng, Chien‐Shan
Wang, Ning
Ren, Junguo
Feng, Yibin
Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p
title Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p
title_full Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p
title_fullStr Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p
title_full_unstemmed Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p
title_short Suppression of lncRNA MALAT1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting IAPs via miR‐22‐3p
title_sort suppression of lncrna malat1 by betulinic acid inhibits hepatocellular carcinoma progression by targeting iaps via mir‐22‐3p
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586994/
https://www.ncbi.nlm.nih.gov/pubmed/33135336
http://dx.doi.org/10.1002/ctm2.190
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