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Long Noncoding RNA ANRIL Promotes Non–Small Cell Lung Cancer Cell Proliferation and Inhibits Apoptosis by Silencing KLF2 and P21 Expression
- Source :
- Molecular Cancer Therapeutics. 14:268-277
- Publication Year :
- 2015
- Publisher :
- American Association for Cancer Research (AACR), 2015.
-
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 p15INK4B, 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. Mol Cancer Ther; 14(1); 268–77. ©2014 AACR.
- Subjects :
- Adult
Cyclin-Dependent Kinase Inhibitor p21
Male
Cancer Research
Lung Neoplasms
Kruppel-Like Transcription Factors
medicine.disease_cause
Mice
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
medicine
Animals
Humans
Gene silencing
Aged
Aged, 80 and over
Regulation of gene expression
Gene knockdown
biology
Cell growth
Neoplasms, Experimental
Middle Aged
Prognosis
Long non-coding RNA
Cell biology
Gene Expression Regulation, Neoplastic
Oncology
Gene Knockdown Techniques
Cancer cell
biology.protein
Female
RNA, Long Noncoding
Carcinogenesis
PRC2
Subjects
Details
- ISSN :
- 15388514 and 15357163
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer Therapeutics
- Accession number :
- edsair.doi.dedup.....490a421a01cad3ec426a2369fef13510