title: The orphan nuclear receptor EAR2 is overexpressed in colorectal cancer and it regulates survivability of colon cancer cells.
abstract: EAR2 is a member of the chick ovalbumin upstream promoter-transcription factors (COUP-TFs). COUP-TFs belong to orphan nuclear receptors and regulate many biological processes. Little is known regarding EAR2 in cancer, though much progress has been made in understanding the function of other COUP-TF members. The aim of this study is to investigate the expression and possible function of EAR2 in colorectal cancer. We determined expression of EAR2 in human primary colorectal malignant tumors and their paired adjacent normal colorectal tissues. We found that expression of EAR2 was upregulated in colorectal tumors. Knockdown of EAR2 induced apoptosis of colon cancer cells, suggesting that EAR2 may function to regulate survivability of colon cancer cells. In vivo tumor study demonstrated that knockdown of EAR2 inhibited the xenograft growth of colon cancer cells. We found that knockdown of EAR2 inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP), suggesting that EAR2 regulates cell survivability, at least partly, through XIAP. In this manuscript, we demonstrated that expression of EAR2 was elevated in colorectal cancer and knockdown of EAR2 reduced survivability and tumor growth of colon cancer cells. Our results suggest that EAR2 plays an important role in development of colorectal cancer. The findings also suggest that EAR2 may serve as a potential therapeutic target of colorectal cancer.
authors.affiliation: The Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xue-Bing
authors.initials: XB
authors.lastname: Li
authors.forename: Shi
authors.initials: S
authors.lastname: Jiao
authors.forename: Heng
authors.initials: H
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Fan
authors.forename: Guo-Hao
authors.initials: GH
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D034741:RNA, Small Interfering; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins; D014183:Transplantation, Heterologous; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C075835:NR2F6 protein, human; D034741:RNA, Small Interfering; D011987:Receptors, Steroid; D012097:Repressor Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein