title: High expression of long non-coding RNA SBF2-AS1 promotes proliferation in non-small cell lung cancer.
abstract: BACKGROUND
  Recent evidence has proven that long noncoding RNAs (lncRNAs) play important roles in cancer biology, while few lncRNAs have been characterized in NSCLC. Here, we characterized a novel lncRNA, SBF2 antisense RNA 1 (SBF2-AS1), in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Quantitative real-time PCR was used to quantify SBF2-AS1 expression in NSCLC tissues and cell lines. The correlation of SBF2-AS1 expression with clinicopathologic features was analyzed in a cohort NSCLC patient. Loss of function and gain of function studies were performed to determine the effects of SBF2-AS1 on proliferation and metastasis of NSCLC cells. RNA immunoprecipitation and chromosome immunoprecipitation assay was performed to confirm the interaction between SBF2-AS1 with protein and chromosome.
  
  
  RESULTS
  We confirmed that SBF2-AS1 was significantly upregulated in NSCLC compared with corresponding non-tumor tissues, and a high expression level of SBF2-AS1 was correlated with lymph node metastasis and advanced TNM stage. Using siRNAs specifically targeting SBF2-AS1 and plasmid vector, we successfully silenced and overexpressed SBF2-AS1 in NSCCLC cell lines and investigated its biological function both in vitro and in vivo. After the silencing of SBF2-AS1, the metastasis of NSCLC cells was significantly inhibited, the silencing of SBF2-AS1 decreased the proliferation of NSCLC cells, and the cell cycle was arrested at the G1 phase; while overexpression promoted proliferation ability. Xenograft tumor models revealed that the silencing of SBF2-AS1 inhibited tumor growth in vivo. We speculated that SBF2-AS1 might negatively regulate P21. RNA immunoprecipitation discovered that SBF2-AS2 could bind with a core component of polycomb repressive complex2, SUZ12. Additionally chromatin immunoprecipitation assay demonstrated that, after silencing SBF2-AS1, the enrichment of SUZ12 and trimethylation of histone 3 lysine 27 decreased at the promoter region of P21.
  
  
  CONCLUSIONS
  We demonstrated that SBF2-AS1 is upregulated in NSCLC and promotes proliferation of NSCLC tumor cells. SBF2-AS1 may serve as a novel biomarker and potential therapeutic target for NSCLC patients.
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 West Beijing Rd, Huai'an, 223300, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, 210009, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, 210000, China.
authors.forename: Mantang
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, 210009, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, 210000, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 West Beijing Rd, Huai'an, 223300, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, 210009, China.
authors.forename: Youtao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, 210009, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 West Beijing Rd, Huai'an, 223300, China.
authors.forename: Xuechun
authors.initials: X
authors.lastname: Leng
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 West Beijing Rd, Huai'an, 223300, China.
authors.forename: Su
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 West Beijing Rd, Huai'an, 223300, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 West Beijing Rd, Huai'an, 223300, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 West Beijing Rd, Huai'an, 223300, China.
authors.forename: Fengqing
authors.initials: F
authors.lastname: Ji
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, 210009, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, 6 West Beijing Rd, Huai'an, 223300, China. keping_xu@163.com.
authors.forename: Keping
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, 210009, China. yinhero001@126.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D062085:RNA, Long Noncoding; C000612825:long non-coding RNA SBF2-AS1, human
keywords: Epigenetic regulation; NSCLC; Proliferation; SBF2-AS1; lncRNA