title: RING1 and YY1 binding protein suppresses breast cancer growth and metastasis.
abstract: Evidence suggests that RING1 and YY1 binding protein (RYBP) functions as a tumor suppressor. However, its role in breast cancer remains unclear. In the present study, the expression of RYBP was assessed in breast cancer patients and cell lines. Disease-free survival durations of breast cancer patients with high RYBP expression were determined based on the ATCG dataset. The effects of RYBP overexpression on cell growth, migration and invasive potency were also assessed. Nude mouse xenograft and lung metastasis models were also used to confirm the role of RYBP. The involvement of SRRM3 in RYBP-mediated breast cancer suppression was explored using SRRM3 siRNA. The potential relationship between RYBP, SRRM3, and REST-003 was examined by qPCR. The results showed that RYBP was downregulated in breast cancer patients and in several breast cancer cell lines. Breast cancer patients with high expression levels of RYBP displayed better disease-free survival. Overexpression of RYBP in MDA-MB-231 and SK-BR-3 cells significantly decreased cell proliferation, migration, and invasion ability, and increased the proportion of cells arrested in S-phase compared with the negative control cells. Additionally, upregulation of proliferation-related cell cycle proteins (cyclin A and cyclin B1) and E-cadherin, and downregulation of snail were observed in RYBP-overexpressing cells. Overexpression of RYBP reduced tumor volume and weight as well as metastatic foci in the lungs of nude mice. SRRM3 knockdown by siRNA, which is downregulated after RYBP overexpression, suppressed cell growth and metastasis in MDA-MB-231 and SK-BR-3 cells. Furthermore, qPCR analysis revealed that REST-003 ncRNA was downregulated in cells overexpressing RYBP and in SRRM3-inhibited cells. Moreover, cell invasion ability and growth were increased after SRRM3 upregulation in RYBP-overexpressing cells, but they were decreased following si-REST-003 transfection. In conclusion, overexpression of RYBP suppresses breast cancer growth and metastasis both in vitro and in vivo. SRRM3 and REST-003, which are downregulated in cells overexpressing RYBP, may be involved in RYBP-mediated breast cancer progression.
authors.affiliation: Department of Neurological Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Zhanqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Runyi
authors.initials: R
authors.lastname: Ye
authors.affiliation: Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shao
authors.affiliation: Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Tuckyun
authors.initials: T
authors.lastname: Cheang
authors.affiliation: Breast and Thyroid Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D056750:Cyclin A1 / Q000096:biosynthesis; D056744:Cyclin B1 / Q000096:biosynthesis; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D050986:YY1 Transcription Factor / Q000378:metabolism; D000099229:RE1-Silencing Transcription Factor
chemical_list: D015820:Cadherins; D056750:Cyclin A1; D056744:Cyclin B1; D047908:Intracellular Signaling Peptides and Proteins; D063150:Polycomb Repressive Complex 1; D011506:Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D050986:YY1 Transcription Factor; D000099229:RE1-Silencing Transcription Factor; C503745:CCNA1 protein, human; C534699:CCNB1 protein, human; C434957:RYBP protein, human; C000608776:SRRM3 protein, human; C494698:YY1 protein, human; C080355:RING1 protein, human