RESUMO
BACKGROUND: Long noncoding RNA ANRIL (antisense non-coding RNA in the INK4 locus) represses p15 and p16, which induce cell-cycle arrest at G1 phase, leading to enhanced cell proliferation of normal fibroblasts. Herein we report that ANRIL is also involved in the regulation of cancer-cell proliferation. MATERIALS AND METHODS: HeLa and H1299 cells were transfected with ANRIL siRNAs. At 72 h post-transfection, cells were subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and cell-cycle analysis. RESULTS: qRT-PCR showed that ANRIL is highly expressed in these cancer cells compared to normal fibroblasts. Depletion of ANRIL increased p15 expression, with no impact on p16 or ARF (alternative reading frame) expression, and caused cell-cycle arrest at the G2/M phase, leading to inhibition of proliferation of H1299 and HeLa cells. CONCLUSION: ANRIL positively regulates the proliferation of cancer cells, such as H1299 and HeLa cells, via regulating p15 and other genes related to G2/M phase control.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidor de Quinase Dependente de Ciclina p15/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Células HeLa , Humanos , Neoplasias Pulmonares/genética , Neoplasias do Colo do Útero/genéticaRESUMO
The p16 tumor suppressor gene encodes a specific inhibitor of cyclin-dependent kinase (CDK) 4 and 6 and is found altered in a wide range of human cancers. p16 plays a pivotal role in tumor suppressor networks through inducing cellular senescence that acts as a barrier to cellular transformation by oncogenic signals. p16 protein is relatively stable and its expression is primary regulated by transcriptional control. Polycomb group (PcG) proteins associate with the p16 locus in a long non-coding RNA, ANRIL-dependent manner, leading to repression of p16 transcription. YB1, a transcription factor, also represses the p16 transcription through direct association with its promoter region. Conversely, the transcription factors Ets1/2 and histone H3K4 methyltransferase MLL1 directly bind to the p16 locus and mediate p16 induction during replicative and premature senescence. In the present review, we discuss the molecular mechanisms by which these factors regulate p16 transcription.