title: Silencing of ZRF1 impedes survival of estrogen receptor positive MCF-7 cells and potentiates the effect of curcumin.
abstract: The role and clinical implication of ZRF1 in breast cancer are poorly understood. So this study is aimed to explore the role of ZRF1 in breast cancer progression. With this context, we first assessed its expression pattern in FFPE primary and metastasis breast tissue samples as well as from publicly available databases. Moreover, we also explored the survival status of patients from the publicly available database and interestingly discover that high expression of ZRF1 decreases the survival of estrogen-positive breast cancer patients more than estrogen-negative status patients. In the perspective of this, we evaluated the role ZRF1 in MCF-7 breast cancer cells and found that it's silencing by knockdown results in decreased cell proliferation as well as cell viability. Results also show that expression of ZRF1 is down regulated in the presence of estrogen-depleted conditions but independent of RAS/MEK as well as AKT axes. Moreover, the decrease in viability of MCF-7 cells was accompanied by induction of apoptosis and DNA damage, well-marked with upregulation of cleaved PARP and downregulation of BCL2 and H2AUbK119 levels. Furthermore, we also explored that knockdown of ZRF1 sensitises the effect of curcumin, observed with decrease in cell viability and dropping of IC50 value from 25 to 15 μM. This investigation thus shed a new light on the role on ZRF1 in breast cancer cells and hence can be exploited to design better therapeutic intervention.
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
authors.forename: Sandip Kumar
authors.initials: SK
authors.lastname: Rath
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.|Cell Signalling Group, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
authors.forename: Moonmoon
authors.initials: M
authors.lastname: Deb
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
authors.forename: Dipta
authors.initials: D
authors.lastname: Sengupta
authors.affiliation: Department of General, Visceral and Pediatric Surgery, University Medical Center, 37075, Göttingen, Germany.
authors.forename: Vijayalaxmi
authors.initials: V
authors.lastname: Kari
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
authors.forename: Swayamsiddha
authors.initials: S
authors.lastname: Kar
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
authors.forename: Sabnam
authors.initials: S
authors.lastname: Parbin
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India.
authors.forename: Nibedita
authors.initials: N
authors.lastname: Pradhan
authors.affiliation: Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, 769008, India. samirp@nitrkl.ac.in.
authors.forename: Samir Kumar
authors.initials: SK
authors.lastname: Patra
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D003474:Curcumin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000032:analysis; D061986:MCF-7 Cells; D018832:Molecular Chaperones; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen / Q000032:analysis*
chemical_list: D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin
keywords: BCL2; Curcumin; Estrogen receptor; PARP; RAS/MEK signalling, H2AUbK119; ZRF1