title: Long noncoding RNA ANRIL promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression.
abstract: Recent evidence highlights long noncoding RNAs (lncRNA) as crucial regulators of cancer biology that contribute to essential cancer cell functions such as cell proliferation, apoptosis, and metastasis. In non-small cell lung cancer (NSCLC), several lncRNAs' expressions are misregulated and have been nominated as critical actors in NSCLC tumorigenesis. LncRNA ANRIL was first found to be required for the PRC2 recruitment to and silencing of p15(INK4B), the expression of which is induced by the ATM-E2F1 signaling pathway. Our previous study showed that ANRIL was significantly upregulated in gastric cancer, and it could promote cell proliferation and inhibit cell apoptosis by silencing of miR99a and miR449a transcription. However, its clinical significance and potential role in NSCLC is still not documented. In this study, we reported that ANRIL expression was increased in NSCLC tissues, and its expression level was significantly correlated with tumor-node-metastasis stages and tumor size. Moreover, patients with high levels of ANRIL expression had a relatively poor prognosis. In addition, taking advantage of loss-of-function experiments in NSCLC cells, we found that knockdown of ANRIL expression could impair cell proliferation and induce cell apoptosis both in vitro and vivo. Furthermore, we uncover that ANRIL could not repress p15 expression in PC9 cells, but through silencing of KLF2 and P21 transcription. Thus, we conclusively demonstrate that lncRNA ANRIL plays a key role in NSCLC development by associating its expression with survival in patients with NSCLC, providing novel insights on the function of lncRNA-driven tumorigenesis.
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Feng-qi
authors.initials: FQ
authors.lastname: Nie
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, People's Republic of China.
authors.forename: Jin-song
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Tong-peng
authors.initials: TP
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Yan-wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xiang-hua
authors.initials: XH
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Er-bao
authors.initials: EB
authors.lastname: Zhang
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China. tgzy111@126.com yongqian_shu@163.com.
authors.forename: Kai-hua
authors.initials: KH
authors.lastname: Lu
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China. tgzy111@126.com yongqian_shu@163.com.
authors.forename: Yong-qian
authors.initials: YQ
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009374:Neoplasms, Experimental; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C493956:CDKN1A protein, human; C561518:CDKN2B antisense RNA, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D062085:RNA, Long Noncoding