title: The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB.
abstract: Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Feng-Qi
authors.initials: FQ
authors.lastname: Nie
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chongshuang
authors.initials: C
authors.lastname: Zang
authors.affiliation: Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jiakai
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. Electronic address: lukaihua110@126.com.
authors.forename: Kai-Hua
authors.initials: KH
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016000:Cluster Analysis; D000072237:ERG1 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D056466:Histone Demethylases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011485:Protein Binding; D011544:Pseudogenes / Q000235:genetics*; D020743:rhoB GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000072237:ERG1 Potassium Channel; D056466:Histone Demethylases; C495195:KDM1A protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D020743:rhoB GTP-Binding Protein
keywords: DUXAP8; EGR1; NSCLC; RHOB; invasion; proliferation; pseudogene