Ras-related associated with diabetes gene acts as a suppressor and inhibits Warburg effect in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide and is a prominent source of mortality. Ras-related associated with diabetes (RRAD), one of the first members of the 35–39 kDa class of novel Ras-related GTPases, is linked to several types of cancer, alth...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
Dove Medical Press
2016
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935086/ |
| id |
pubmed-4935086 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-49350862016-07-14 Ras-related associated with diabetes gene acts as a suppressor and inhibits Warburg effect in hepatocellular carcinoma Yan, Yingcai Xie, Minjie Zhang, Linshi Zhou, Xiaohu Xie, Haiyang Zhou, Lin Zheng, Shusen Wang, Weilin Original Research Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide and is a prominent source of mortality. Ras-related associated with diabetes (RRAD), one of the first members of the 35–39 kDa class of novel Ras-related GTPases, is linked to several types of cancer, although its function in HCC remains unclear. In this study, we observed that RRAD was downregulated in HCC compared with adjacent normal tissues. This change was associated with a poor prognosis. Furthermore, knockdown of RRAD in SK-Hep-1 cells facilitated cell proliferation, accelerated the G1/S transition during the cell cycle, induced cell migration, and reduced apoptosis. In contrast, overexpression of RRAD in Huh7 cells had the opposite effects. Moreover, we demonstrated that RRAD induced cell proliferation through regulation of the cell cycle by downregulating cyclins and cyclin-dependent kinases. RRAD induced tumor cell apoptosis through the mitochondrial apoptosis pathway. In addition, we confirmed that knockdown of RRAD promoted aerobic glycolysis by upregulating glucose transporter 1, whereas overexpression of RRAD inhibited aerobic glycolysis. In conclusion, RRAD plays a pivotal role as a potential tumor suppressor in HCC. An improved understanding of the roles of RRAD in tumor metabolism may provide insights into its potential as a novel molecular target in HCC therapy. Dove Medical Press 2016-06-30 /pmc/articles/PMC4935086/ /pubmed/27418837 http://dx.doi.org/10.2147/OTT.S106703 Text en © 2016 Yan et al. 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Yan, Yingcai Xie, Minjie Zhang, Linshi Zhou, Xiaohu Xie, Haiyang Zhou, Lin Zheng, Shusen Wang, Weilin |
| spellingShingle |
Yan, Yingcai Xie, Minjie Zhang, Linshi Zhou, Xiaohu Xie, Haiyang Zhou, Lin Zheng, Shusen Wang, Weilin Ras-related associated with diabetes gene acts as a suppressor and inhibits Warburg effect in hepatocellular carcinoma |
| author_facet |
Yan, Yingcai Xie, Minjie Zhang, Linshi Zhou, Xiaohu Xie, Haiyang Zhou, Lin Zheng, Shusen Wang, Weilin |
| author_sort |
Yan, Yingcai |
| title |
Ras-related associated with diabetes gene acts as a suppressor and inhibits Warburg effect in hepatocellular carcinoma |
| title_short |
Ras-related associated with diabetes gene acts as a suppressor and inhibits Warburg effect in hepatocellular carcinoma |
| title_full |
Ras-related associated with diabetes gene acts as a suppressor and inhibits Warburg effect in hepatocellular carcinoma |
| title_fullStr |
Ras-related associated with diabetes gene acts as a suppressor and inhibits Warburg effect in hepatocellular carcinoma |
| title_full_unstemmed |
Ras-related associated with diabetes gene acts as a suppressor and inhibits Warburg effect in hepatocellular carcinoma |
| title_sort |
ras-related associated with diabetes gene acts as a suppressor and inhibits warburg effect in hepatocellular carcinoma |
| description |
Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide and is a prominent source of mortality. Ras-related associated with diabetes (RRAD), one of the first members of the 35–39 kDa class of novel Ras-related GTPases, is linked to several types of cancer, although its function in HCC remains unclear. In this study, we observed that RRAD was downregulated in HCC compared with adjacent normal tissues. This change was associated with a poor prognosis. Furthermore, knockdown of RRAD in SK-Hep-1 cells facilitated cell proliferation, accelerated the G1/S transition during the cell cycle, induced cell migration, and reduced apoptosis. In contrast, overexpression of RRAD in Huh7 cells had the opposite effects. Moreover, we demonstrated that RRAD induced cell proliferation through regulation of the cell cycle by downregulating cyclins and cyclin-dependent kinases. RRAD induced tumor cell apoptosis through the mitochondrial apoptosis pathway. In addition, we confirmed that knockdown of RRAD promoted aerobic glycolysis by upregulating glucose transporter 1, whereas overexpression of RRAD inhibited aerobic glycolysis. In conclusion, RRAD plays a pivotal role as a potential tumor suppressor in HCC. An improved understanding of the roles of RRAD in tumor metabolism may provide insights into its potential as a novel molecular target in HCC therapy. |
| publisher |
Dove Medical Press |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4935086/ |
| _version_ |
1613605147576893440 |