title: Two Splice Variants of Y Chromosome-Located Lysine-Specific Demethylase 5D Have Distinct Function in Prostate Cancer Cell Line (DU-145).
abstract: One of the major objectives of the Human Y Chromosome Proteome Project is to characterize sets of proteins encoded from the human Y chromosome. Lysine (K)-specific demethylase 5D (KDM5D) is located on the AZFb region of the Y chromosome and encodes a JmjC-domain-containing protein. KDM5D, the least well-documented member of the KDM5 family, is capable of demethylating di- and trimethyl H3K4. In this study, we detected two novel splice variants of KDM5D with lengths of 2650bp and 2400bp that correspond to the 100 and 80 kDa proteins in the human prostate cancer cell line, DU-145. The knockdown of two variants using the short interfering RNA (siRNA) approach increased the growth rate of prostate cancer cells and reduced cell apoptosis. To explore the proteome pattern of the cells after KDM5D downregulation, we applied a shotgun label-free quantitative proteomics approach. Of 820 proteins present in all four replicates of two treatments, the abundance of 209 proteins changed significantly in response to KDM5D suppression. Of these, there were 102 proteins observed to be less abundant and 107 more abundant in KDM5D knockdown cells compared with control cells. The results revealed that KDM5D knockdown altered the abundance of proteins involved in RNA processing, protein synthesis, apoptosis, the cell cycle, and growth and proliferation. In conjunction, these results provided new insights into the function of KDM5D and its splice variants. The proteomics data are available at PRIDE with ProteomeXchange identifier PXD000416.
authors.affiliation: Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.|Biochemistry Department, Iran University of Medical Sciences , Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Jangravi
authors.affiliation: Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.
authors.forename: Mehdi Sharif
authors.initials: MS
authors.lastname: Tabar
authors.affiliation: The Australian School of Advanced Medicine, Faculty of Human Sciences, Macquarie University , Sydney, New South Wales 2109, Australia.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mirzaei
authors.affiliation: Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.
authors.forename: Pouria
authors.initials: P
authors.lastname: Parsamatin
authors.affiliation: Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.
authors.forename: Haghighat
authors.initials: H
authors.lastname: Vakilian
authors.affiliation: Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Alikhani
authors.affiliation: Biochemistry Department, Iran University of Medical Sciences , Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shabani
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University , Sydney, New South Wales 2109, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Haynes
authors.affiliation: The Australian School of Advanced Medicine, Faculty of Human Sciences, Macquarie University , Sydney, New South Wales 2109, Australia.
authors.forename: Ann K
authors.initials: AK
authors.lastname: Goodchild
authors.affiliation: Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR , Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Gourabi
authors.affiliation: Department of Developmental Biology, University of Science and Culture, ACECR , Tehran, Iran.|Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
authors.affiliation: Molecular Systems Biology Department at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR , Tehran, Iran.|Department of Systems Biology, Agricultural Biotechnology Research Institute of Iran , Karaj, Iran.
authors.forename: Ghasem Hosseini
authors.initials: GH
authors.lastname: Salekdeh
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D041322:Chromosomes, Human, Y; D015536:Down-Regulation; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D011471:Prostatic Neoplasms / Q000201:enzymology*; D034741:RNA, Small Interfering / Q000235:genetics; D053719:Tandem Mass Spectrometry
chemical_list: D015778:Minor Histocompatibility Antigens; D034741:RNA, Small Interfering; D056466:Histone Demethylases; C095561:KDM5D protein, human
keywords: Human Proteome Project; lysine (K)-specific demethylase 5D (KDM5D); short interfering RNA (siRNA); shotgun proteomics