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Regulation of the sensitivity of hepatocarcinoma cells by ORMDL3, to sorafenib by autophagy
Serum orosomucoid1-like protein 3 (ORMDL3) is a membrane protein in the endoplasmic reticulum, known to regulate many important signal transduction processes and autophagy regulation, but it is unclear whether it is involved in the intratumoral microenvironment and cancer drug resistance. Our presen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381447/ https://www.ncbi.nlm.nih.gov/pubmed/35972600 http://dx.doi.org/10.1007/s12032-022-01767-z |
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author | Sun, Yixiao Guan, Xueran Zhang, Ting Li, Yue Shi, Huiling Chitakunye, Ashleigh Tinotenda Hong, Hanyu Zhang, Shihui Zhu, Qin Cai, Lin |
author_facet | Sun, Yixiao Guan, Xueran Zhang, Ting Li, Yue Shi, Huiling Chitakunye, Ashleigh Tinotenda Hong, Hanyu Zhang, Shihui Zhu, Qin Cai, Lin |
author_sort | Sun, Yixiao |
collection | PubMed |
description | Serum orosomucoid1-like protein 3 (ORMDL3) is a membrane protein in the endoplasmic reticulum, known to regulate many important signal transduction processes and autophagy regulation, but it is unclear whether it is involved in the intratumoral microenvironment and cancer drug resistance. Our present study found that silencing ORMDL3 increases the inhibitory effect of sorafenib on the viability and proliferation in HCC cells, and increases the sensitivity of HCC cells to sorafenib. In addition, silencing ORMDL3 can increase ROS levels by inhibiting autophagy, thereby increasing sorafenib-induced apoptosis of HCC cells. Further, our study also found that ORMDL3 silencing inhibits autophagy through the PERK-ATF4-Beclin1 pathway, thus affecting sorafenib sensitivity. The in vivo effects of sorafenib were tested by xenografting using nude mice. It showed that silencing ORMDL3 in HCC cells could increase the inhibitory effect of sorafenib on the growth of tumors. This is the first report to describe the relationships among ORMDL3, autophagy, and sorafenib resistance. This study provides available targets that might have a synergetic effect with sorafenib. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12032-022-01767-z. |
format | Online Article Text |
id | pubmed-9381447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-93814472022-08-18 Regulation of the sensitivity of hepatocarcinoma cells by ORMDL3, to sorafenib by autophagy Sun, Yixiao Guan, Xueran Zhang, Ting Li, Yue Shi, Huiling Chitakunye, Ashleigh Tinotenda Hong, Hanyu Zhang, Shihui Zhu, Qin Cai, Lin Med Oncol Original Paper Serum orosomucoid1-like protein 3 (ORMDL3) is a membrane protein in the endoplasmic reticulum, known to regulate many important signal transduction processes and autophagy regulation, but it is unclear whether it is involved in the intratumoral microenvironment and cancer drug resistance. Our present study found that silencing ORMDL3 increases the inhibitory effect of sorafenib on the viability and proliferation in HCC cells, and increases the sensitivity of HCC cells to sorafenib. In addition, silencing ORMDL3 can increase ROS levels by inhibiting autophagy, thereby increasing sorafenib-induced apoptosis of HCC cells. Further, our study also found that ORMDL3 silencing inhibits autophagy through the PERK-ATF4-Beclin1 pathway, thus affecting sorafenib sensitivity. The in vivo effects of sorafenib were tested by xenografting using nude mice. It showed that silencing ORMDL3 in HCC cells could increase the inhibitory effect of sorafenib on the growth of tumors. This is the first report to describe the relationships among ORMDL3, autophagy, and sorafenib resistance. This study provides available targets that might have a synergetic effect with sorafenib. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12032-022-01767-z. Springer US 2022-08-16 2022 /pmc/articles/PMC9381447/ /pubmed/35972600 http://dx.doi.org/10.1007/s12032-022-01767-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/) . |
spellingShingle | Original Paper Sun, Yixiao Guan, Xueran Zhang, Ting Li, Yue Shi, Huiling Chitakunye, Ashleigh Tinotenda Hong, Hanyu Zhang, Shihui Zhu, Qin Cai, Lin Regulation of the sensitivity of hepatocarcinoma cells by ORMDL3, to sorafenib by autophagy |
title | Regulation of the sensitivity of hepatocarcinoma cells by ORMDL3, to sorafenib by autophagy |
title_full | Regulation of the sensitivity of hepatocarcinoma cells by ORMDL3, to sorafenib by autophagy |
title_fullStr | Regulation of the sensitivity of hepatocarcinoma cells by ORMDL3, to sorafenib by autophagy |
title_full_unstemmed | Regulation of the sensitivity of hepatocarcinoma cells by ORMDL3, to sorafenib by autophagy |
title_short | Regulation of the sensitivity of hepatocarcinoma cells by ORMDL3, to sorafenib by autophagy |
title_sort | regulation of the sensitivity of hepatocarcinoma cells by ormdl3, to sorafenib by autophagy |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381447/ https://www.ncbi.nlm.nih.gov/pubmed/35972600 http://dx.doi.org/10.1007/s12032-022-01767-z |
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