title: Long Noncoding RNA LINC00673 Is Activated by SP1 and Exerts Oncogenic Properties by Interacting with LSD1 and EZH2 in Gastric Cancer.
abstract: Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the biological function of these molecules and the mechanisms responsible for their alteration in gastric cancer (GC) are not fully understood. In this study, we found that lncRNA LINC00673 is significantly upregulated in gastric cancer. Knockdown of LINC00673 inhibited cell proliferation and invasion and induced cell apoptosis, whereas LINC00673 overexpression had the opposite effect. Online transcription factor binding site prediction analysis showed that there are SP1 binding sites in the LINC00673 promoter region. Next, luciferase reporter and chromatin immunoprecipitation (ChIP) assays provided evidence that SP1 could bind directly to the LINC00673 promoter region and activate its transcription. Moreover, mechanistic investigation showed that CADM4, KLF2, and LATS2 might be the underlying targets of LINC00673 in GC cells, and RNA immunoprecipitation, RNA pull-down, and ChIP assays showed that LINC00673 can interact with EZH2 and LSD1, thereby repressing KLF2 and LATS2 expression. Taken together, these findings show that SP1-activated LINC00673 exerts an oncogenic function that promotes GC development and progression, at least in part, by functioning as a scaffold for LSD1 and EZH2 and repressing KLF2 and LATS2 expression.
authors.affiliation: Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, People's Republic of China; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Mingde
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jiakai
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210011, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210011, People's Republic of China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210011, People's Republic of China. Electronic address: 957714486@qq.com.
authors.forename: Fengqi
authors.initials: F
authors.lastname: Nie
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210011, People's Republic of China. Electronic address: zhaoxiawang88@hotmail.com.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: msun7@mdanderson.org.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics*; D004843:Epistasis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009857:Oncogenes; D011379:Prognosis; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015533:Transcriptional Activation
chemical_list: D062085:RNA, Long Noncoding; D016329:Sp1 Transcription Factor; D056466:Histone Demethylases; C495195:KDM1A protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: LINC00673; cell growth; gastric cancer; lncRNA; metastasis