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HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and chemoresistance is the main obstacle for effective treatments of HCC. Accumulating studies indicated that long non-coding RNAs (lncRNAs) contribute to the chemoresistance of human carcinoma. However, the...

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Autores principales: Shi, Yang, Yang, Xiaohua, Xue, Xiaofeng, Sun, Ding, Cai, Peng, Song, Qingwei, Zhang, Bin, Qin, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069583/
https://www.ncbi.nlm.nih.gov/pubmed/32210579
http://dx.doi.org/10.2147/OTT.S229913
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author Shi, Yang
Yang, Xiaohua
Xue, Xiaofeng
Sun, Ding
Cai, Peng
Song, Qingwei
Zhang, Bin
Qin, Lei
author_facet Shi, Yang
Yang, Xiaohua
Xue, Xiaofeng
Sun, Ding
Cai, Peng
Song, Qingwei
Zhang, Bin
Qin, Lei
author_sort Shi, Yang
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and chemoresistance is the main obstacle for effective treatments of HCC. Accumulating studies indicated that long non-coding RNAs (lncRNAs) contribute to the chemoresistance of human carcinoma. However, the functional role of HANR in autophagy-mediated chemoresistance of HCC is unknown. METHODS: The expressions of HANR, miR-29b and ATG9A in tissues and cell lines were detected by real-time quantitative PCR (RT-qPCR). The expression of autophagy-related protein LC3-I and LC3-II was evaluated by Western blotting. The cell viability and apoptosis were examined by CCK-8 and flow cytometry, respectively. Bioinformatics analysis and luciferase activity assay were applied to determine the downstream target gene of HANR or miR-29b. Xenograft experiment was used to detect the effect of HANR on tumor growth. RESULTS: In the present study, we demonstrated that HANR was notably overexpressed in sorafenib-resistant HepG2 (HepG2/sora) and sorafenib-resistant Huh7 (Huh7/sora) cells, and HANR enhanced sorafenib resistance by facilitating autophagy in HepG2/sora and Huh7/sora cells. Furthermore, we demonstrated that miR‑29b could directly interact with HANR and abolished HANR-induced sorafenib resistance by suppressing autophagy in HepG2/sora and Huh7/sora cells. Moreover, ATG9A was validated as a target of miR-29b and its overexpression obviously reversed the inhibitory effect of miR-29b on sorafenib resistance and autophagy. In addition, HANR could act as a competing endogenous RNA (ceRNA) to upregulate ATG9A expression by sponging miR-29b. Hence, HANR increased autophagy-related sorafenib resistance via inhibiting the miR-29b/ATG9A axis in HepG2/sora and Huh7/sora cells, indicating that it may be a potential target to prevent chemoresistance of HCC. CONCLUSION: Our study revealed HANR enhanced sorafenib resistance by acting as an autophagy promoter by regulating miR-29b/ATG9A axis in sorafenib‑resistant HCC cells and might provide potential therapeutic strategies for HCC treatment.
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spelling pubmed-70695832020-03-24 HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma Shi, Yang Yang, Xiaohua Xue, Xiaofeng Sun, Ding Cai, Peng Song, Qingwei Zhang, Bin Qin, Lei Onco Targets Ther Original Research BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and chemoresistance is the main obstacle for effective treatments of HCC. Accumulating studies indicated that long non-coding RNAs (lncRNAs) contribute to the chemoresistance of human carcinoma. However, the functional role of HANR in autophagy-mediated chemoresistance of HCC is unknown. METHODS: The expressions of HANR, miR-29b and ATG9A in tissues and cell lines were detected by real-time quantitative PCR (RT-qPCR). The expression of autophagy-related protein LC3-I and LC3-II was evaluated by Western blotting. The cell viability and apoptosis were examined by CCK-8 and flow cytometry, respectively. Bioinformatics analysis and luciferase activity assay were applied to determine the downstream target gene of HANR or miR-29b. Xenograft experiment was used to detect the effect of HANR on tumor growth. RESULTS: In the present study, we demonstrated that HANR was notably overexpressed in sorafenib-resistant HepG2 (HepG2/sora) and sorafenib-resistant Huh7 (Huh7/sora) cells, and HANR enhanced sorafenib resistance by facilitating autophagy in HepG2/sora and Huh7/sora cells. Furthermore, we demonstrated that miR‑29b could directly interact with HANR and abolished HANR-induced sorafenib resistance by suppressing autophagy in HepG2/sora and Huh7/sora cells. Moreover, ATG9A was validated as a target of miR-29b and its overexpression obviously reversed the inhibitory effect of miR-29b on sorafenib resistance and autophagy. In addition, HANR could act as a competing endogenous RNA (ceRNA) to upregulate ATG9A expression by sponging miR-29b. Hence, HANR increased autophagy-related sorafenib resistance via inhibiting the miR-29b/ATG9A axis in HepG2/sora and Huh7/sora cells, indicating that it may be a potential target to prevent chemoresistance of HCC. CONCLUSION: Our study revealed HANR enhanced sorafenib resistance by acting as an autophagy promoter by regulating miR-29b/ATG9A axis in sorafenib‑resistant HCC cells and might provide potential therapeutic strategies for HCC treatment. Dove 2020-03-09 /pmc/articles/PMC7069583/ /pubmed/32210579 http://dx.doi.org/10.2147/OTT.S229913 Text en © 2020 Shi et al. http://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/). 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
Shi, Yang
Yang, Xiaohua
Xue, Xiaofeng
Sun, Ding
Cai, Peng
Song, Qingwei
Zhang, Bin
Qin, Lei
HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma
title HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma
title_full HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma
title_fullStr HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma
title_full_unstemmed HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma
title_short HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma
title_sort hanr enhances autophagy-associated sorafenib resistance through mir-29b/atg9a axis in hepatocellular carcinoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069583/
https://www.ncbi.nlm.nih.gov/pubmed/32210579
http://dx.doi.org/10.2147/OTT.S229913
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