Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway
Abstract Background To examine the influence of HOXD10 on the metabolism and growth of colon carcinoma cells by suppressing the RHOC/AKT/MAPK pathway. Methods Thirty-seven paired colon cancer and its adjacent samples from The Cancer Genome Atlas (TCGA) were analyzed. Chip Analysis Methylation Pipeli...
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doaj-61cef43f577e4c8386d5b167eba5dc742020-11-25T01:31:02ZengBMCCell Communication and Signaling1478-811X2019-01-0117111310.1186/s12964-018-0316-0Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathwayYu-hong Yuan0Han-yu Wang1Yu Lai2Wa Zhong3Wei-ling Liang4Fu-de Yan5Zhong Yu6Jun-kai Chen7Ying Lin8Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer CenterDepartment of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Internal Medicine, Luopu Community Health Service Center of Panyu DistrictDepartment of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityAbstract Background To examine the influence of HOXD10 on the metabolism and growth of colon carcinoma cells by suppressing the RHOC/AKT/MAPK pathway. Methods Thirty-seven paired colon cancer and its adjacent samples from The Cancer Genome Atlas (TCGA) were analyzed. Chip Analysis Methylation Pipeline (ChAMP) analysis was employed for differential methylated points (DMPs) and the differential methylation regions (DMRs) screening. The HOXD10 mRNA expression and DNA methylation levels were detected by RT-PCR. The Cell proliferation, migration, invasion and apoptosis were respectively measured by MTT assay, transwell assay, wound healing assay and flow cytometry assay in carcinoma cell lines after treated with 5-aza-2′-deoxycytidine (5-Aza-dC) or transfected with HOXD10-expressing plasmid. The expression of HOXD10 and RHOC was revealed by immunohistochemistry in disparate differentiation colon carcinoma tissues, and the dephosphorylation of AKT and MAPK pathways were detected by RT-PCR and western blot. Results The bioinformatics analysis demonstrated that HOXD10 was hypermethylated and low-expressed in colorectal cancer tissues. The detection of RT-PCR indicated the similar results in colorectal cancer cell lines and tissues. The induction of demethylation was recovered by treatment with 5-Aza-dC and the HOXD10 in colorectal cancer cell lines was re-expressed by transfection with a HOXD10 expression vector. The demethylation or overexpression of HOXD10 suppressed proliferation, migration, invasion and promoted apoptosis in colorectal cancer cells. HXOD10 suppressed the tumor growth and detected an opposite trend of protein RHOC. AKT and MAPK pathways were notably inactivated after the dephosphorylation due to the overexpression of HOXD10. Conclusions HOXD10 was suppressed in colon adenocarcinoma cells, which down-regulated RHOC/AKT/MAPK pathway to enhance colon cancer cells apoptosis and constrain the proliferation, migration and invasion.http://link.springer.com/article/10.1186/s12964-018-0316-0Colon cancerMethylation5-Aza-dCHOXD10RHOC/AKT/MAPK pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu-hong Yuan Han-yu Wang Yu Lai Wa Zhong Wei-ling Liang Fu-de Yan Zhong Yu Jun-kai Chen Ying Lin |
spellingShingle |
Yu-hong Yuan Han-yu Wang Yu Lai Wa Zhong Wei-ling Liang Fu-de Yan Zhong Yu Jun-kai Chen Ying Lin Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway Cell Communication and Signaling Colon cancer Methylation 5-Aza-dC HOXD10 RHOC/AKT/MAPK pathway |
author_facet |
Yu-hong Yuan Han-yu Wang Yu Lai Wa Zhong Wei-ling Liang Fu-de Yan Zhong Yu Jun-kai Chen Ying Lin |
author_sort |
Yu-hong Yuan |
title |
Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway |
title_short |
Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway |
title_full |
Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway |
title_fullStr |
Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway |
title_full_unstemmed |
Epigenetic inactivation of HOXD10 is associated with human colon cancer via inhibiting the RHOC/AKT/MAPK signaling pathway |
title_sort |
epigenetic inactivation of hoxd10 is associated with human colon cancer via inhibiting the rhoc/akt/mapk signaling pathway |
publisher |
BMC |
series |
Cell Communication and Signaling |
issn |
1478-811X |
publishDate |
2019-01-01 |
description |
Abstract Background To examine the influence of HOXD10 on the metabolism and growth of colon carcinoma cells by suppressing the RHOC/AKT/MAPK pathway. Methods Thirty-seven paired colon cancer and its adjacent samples from The Cancer Genome Atlas (TCGA) were analyzed. Chip Analysis Methylation Pipeline (ChAMP) analysis was employed for differential methylated points (DMPs) and the differential methylation regions (DMRs) screening. The HOXD10 mRNA expression and DNA methylation levels were detected by RT-PCR. The Cell proliferation, migration, invasion and apoptosis were respectively measured by MTT assay, transwell assay, wound healing assay and flow cytometry assay in carcinoma cell lines after treated with 5-aza-2′-deoxycytidine (5-Aza-dC) or transfected with HOXD10-expressing plasmid. The expression of HOXD10 and RHOC was revealed by immunohistochemistry in disparate differentiation colon carcinoma tissues, and the dephosphorylation of AKT and MAPK pathways were detected by RT-PCR and western blot. Results The bioinformatics analysis demonstrated that HOXD10 was hypermethylated and low-expressed in colorectal cancer tissues. The detection of RT-PCR indicated the similar results in colorectal cancer cell lines and tissues. The induction of demethylation was recovered by treatment with 5-Aza-dC and the HOXD10 in colorectal cancer cell lines was re-expressed by transfection with a HOXD10 expression vector. The demethylation or overexpression of HOXD10 suppressed proliferation, migration, invasion and promoted apoptosis in colorectal cancer cells. HXOD10 suppressed the tumor growth and detected an opposite trend of protein RHOC. AKT and MAPK pathways were notably inactivated after the dephosphorylation due to the overexpression of HOXD10. Conclusions HOXD10 was suppressed in colon adenocarcinoma cells, which down-regulated RHOC/AKT/MAPK pathway to enhance colon cancer cells apoptosis and constrain the proliferation, migration and invasion. |
topic |
Colon cancer Methylation 5-Aza-dC HOXD10 RHOC/AKT/MAPK pathway |
url |
http://link.springer.com/article/10.1186/s12964-018-0316-0 |
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