title: Upregulated long non-coding RNA AGAP2-AS1 represses LATS2 and KLF2 expression through interacting with EZH2 and LSD1 in non-small-cell lung cancer cells.
abstract: Recently, long non-coding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes, including cell proliferation, differentiation and cancer cells metastasis. Accumulating evidence has revealed that aberrant lncRNA expression plays important roles in carcinogenesis and tumor progression. However, the expression pattern and biological function of lncRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. In this study, we performed comprehensive analysis of lncRNA expression in human NSCLC samples by using microarray data from Gene Expression Omnibus. After validation in a cohort of 80 pairs of NSCLC tissues, we identified a differentially expressed novel oncogenic lncRNA termed as AGAP2-AS1. The AGAP2-AS1 expression level was significantly upregulated in NSCLC tissues and negatively correlated with poor prognostic outcomes in patients. In vitro loss- and gain-of-function assays revealed that AGAP2-AS1 knockdown inhibited cell proliferation, migration and invasion, and induced cell apoptosis. In vivo assays also confirmed the ability of AGAP2-AS1 to promote tumor growth. Furthermore, mechanistic investigation showed that AGAP2-AS1 could bind with enhancer of zeste homolog 2 and lysine (K)-specific demethylase 1A, and recruit them to KLF2 and LATS2 promoter regions to repress their transcription. Taken together, our findings indicate that AGAP2-AS1 may act as an oncogene by repressing tumor-suppressor LATS2 and KLF2 transcription. By clarifying the AGAP2-AS1 mechanisms underlying NSCLC development and progression, these findings might promote the development of novel therapeutic strategies for this disease.
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Zang
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: P
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pathology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000368:Aged; D017209:Apoptosis; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D020320:Oligoribonucleotides, Antisense; D062085:RNA, Long Noncoding; D025521:Tumor Suppressor Proteins; D056466:Histone Demethylases; C495195:KDM1A protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases