Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development
Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer related death worldwide. This study was designed to find tumor suppressors involved in CRC development by performing RNA-seq. Eight CRC cell lines and 130 cases of primary CRC samples were used. RN...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-07-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2017.1341027 |
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| author | Dan Gao Yingjie Han Yang Yang James G. Herman Enqiang Linghu Qimin Zhan François Fuks Zhi John Lu Mingzhou Guo |
| author_facet | Dan Gao Yingjie Han Yang Yang James G. Herman Enqiang Linghu Qimin Zhan François Fuks Zhi John Lu Mingzhou Guo |
| author_sort | Dan Gao |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer related death worldwide. This study was designed to find tumor suppressors involved in CRC development by performing RNA-seq. Eight CRC cell lines and 130 cases of primary CRC samples were used. RNA-seq, methylation-specific PCR (MSP), flow cytometry, transwell assays, and a xenograft mouse model were used. Reduction of TMEM176A expression was confirmed in human CRC cells by RNA-seq. TMEM176A was expressed in LS180 and SW620 cells, loss of TMEM176A expression was observed in LOVO, HCT116, RKO, and DLD1 cells, and reduced TMEM176A expression was found in HT29 and SW480 cells. Unmethylation of the TMEM176A promoter was found in LS180 and SW620 cells, whereas complete methylation was found in LOVO, HCT116, RKO, and DLD1 cells, and partial methylation was found in HT29 and SW480 cells. Promoter region methylation correlated with loss of/reduced expression of TMEM176A. Re-expression of TMEM176A was induced by 5-aza-2′-deoxycytidine. TMEM176A was methylated in 50.77% of primary colorectal cancers. Methylation of TMEM176A was associated with tumor metastasis (P<0.05) and was an independent prognostic factor for 5-year overall survival (OS) according to Cox proportional hazards model analysis (P<0.05). TMEM176A induced apoptosis and inhibited cell migration and invasion in CRC cells. TMEM176A suppressed CRC cell growth both in vitro and in vivo. Our results suggest that expression of TMEM176A is regulated by promoter region methylation. TMEM176A methylation is an independent prognostic marker for 5-year OS in CRC, and may act as a tumor suppressor in CRC. |
| first_indexed | 2024-03-11T23:07:09Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:09Z |
| publishDate | 2017-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-16f3ea793baf49c3a1c58cdb30dba4132023-09-21T12:43:13ZengTaylor & Francis GroupEpigenetics1559-22941559-23082017-07-0112757558310.1080/15592294.2017.13410271341027Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer developmentDan Gao0Yingjie Han1Yang Yang2James G. Herman3Enqiang Linghu4Qimin Zhan5François Fuks6Zhi John Lu7Mingzhou Guo8Chinese PLA General HospitalChinese PLA General HospitalMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua UniversityThe Hillman Cancer Center, University of Pittsburgh Cancer InstituteChinese PLA General HospitalPeking University Cancer Hospital & InstituteFree University of Brussels (U.L.B.)MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua UniversityChinese PLA General HospitalColorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer related death worldwide. This study was designed to find tumor suppressors involved in CRC development by performing RNA-seq. Eight CRC cell lines and 130 cases of primary CRC samples were used. RNA-seq, methylation-specific PCR (MSP), flow cytometry, transwell assays, and a xenograft mouse model were used. Reduction of TMEM176A expression was confirmed in human CRC cells by RNA-seq. TMEM176A was expressed in LS180 and SW620 cells, loss of TMEM176A expression was observed in LOVO, HCT116, RKO, and DLD1 cells, and reduced TMEM176A expression was found in HT29 and SW480 cells. Unmethylation of the TMEM176A promoter was found in LS180 and SW620 cells, whereas complete methylation was found in LOVO, HCT116, RKO, and DLD1 cells, and partial methylation was found in HT29 and SW480 cells. Promoter region methylation correlated with loss of/reduced expression of TMEM176A. Re-expression of TMEM176A was induced by 5-aza-2′-deoxycytidine. TMEM176A was methylated in 50.77% of primary colorectal cancers. Methylation of TMEM176A was associated with tumor metastasis (P<0.05) and was an independent prognostic factor for 5-year overall survival (OS) according to Cox proportional hazards model analysis (P<0.05). TMEM176A induced apoptosis and inhibited cell migration and invasion in CRC cells. TMEM176A suppressed CRC cell growth both in vitro and in vivo. Our results suggest that expression of TMEM176A is regulated by promoter region methylation. TMEM176A methylation is an independent prognostic marker for 5-year OS in CRC, and may act as a tumor suppressor in CRC.http://dx.doi.org/10.1080/15592294.2017.1341027colorectal cancerdna methylationmetastasisprognosistmem176a |
| spellingShingle | Dan Gao Yingjie Han Yang Yang James G. Herman Enqiang Linghu Qimin Zhan François Fuks Zhi John Lu Mingzhou Guo Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development Epigenetics colorectal cancer dna methylation metastasis prognosis tmem176a |
| title | Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development |
| title_full | Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development |
| title_fullStr | Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development |
| title_full_unstemmed | Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development |
| title_short | Methylation of TMEM176A is an independent prognostic marker and is involved in human colorectal cancer development |
| title_sort | methylation of tmem176a is an independent prognostic marker and is involved in human colorectal cancer development |
| topic | colorectal cancer dna methylation metastasis prognosis tmem176a |
| url | http://dx.doi.org/10.1080/15592294.2017.1341027 |
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