title: Integrated genomic analyses identify KDM1A's role in cell proliferation via modulating E2F signaling activity and associate with poor clinical outcome in oral cancer.
abstract: The histone demethylase KDM1A specifically demethylates lysine residues and its deregulation has been implicated in the initiation and progression of various cancers. However, KDM1A's molecular role and its pathological consequences, and prognostic significance in oral cancer remain less understood. In the present study, we sought to investigate the expression of KDM1A and its downstream role in oral cancer pathogenesis. By comparing mRNA expression profiles, we identified an elevated KDM1A expression in oral tumors when compared to normal oral tissues. In silico pathway prediction identified the association between KDM1A and E2F1 signaling in oral cancer. Pathway scanning, functional annotation analysis and In vitro assays showed the KDM1A's involvement in oral cancer cell proliferation and the cell cycle. Moreover, real time PCR and luciferase assays confirmed KDM1A's role in regulation of E2F1 signaling activity in oral cancer. Elevated KDM1A expression is associated with poor clinical outcome in oral cancer. Our data indicate that deregulated KDM1A expression is positively associated with proliferative phenotype of oral cancer and confers poor clinical outcome. These cumulative data suggest that KDM1A might be a potential diagnostic and therapeutic target for oral cancer.
authors.affiliation: Epigenetics and RNA Processing Laboratory (ERPL), Indian Institute of Science Education and Research Bhopal (IISERB), Madhya Pradesh, India.
authors.forename: Sathiya Pandi
authors.initials: SP
authors.lastname: Narayanan
authors.affiliation: Epigenetics and RNA Processing Laboratory (ERPL), Indian Institute of Science Education and Research Bhopal (IISERB), Madhya Pradesh, India.
authors.forename: Smriti
authors.initials: S
authors.lastname: Singh
authors.affiliation: Epigenetics and RNA Processing Laboratory (ERPL), Indian Institute of Science Education and Research Bhopal (IISERB), Madhya Pradesh, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Epigenetics and RNA Processing Laboratory (ERPL), Indian Institute of Science Education and Research Bhopal (IISERB), Madhya Pradesh, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Yadav
authors.affiliation: Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: singhshr@mail.nih.gov.
authors.forename: Shree Ram
authors.initials: SR
authors.lastname: Singh
authors.affiliation: Epigenetics and RNA Processing Laboratory (ERPL), Indian Institute of Science Education and Research Bhopal (IISERB), Madhya Pradesh, India. Electronic address: sanjeevs@iiserb.ac.in.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Shukla
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003198:Computer Simulation; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D012333:RNA, Messenger; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Cell proliferation; E2F1 signaling; Histone demethylase; KDM1A; Oral cancer