LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
Abstract Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We anal...
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| Autores principales: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2018
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/3ba9c4d7802b420d8db868eb1877473f |
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| Sumario: | Abstract Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P < 0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P = 0.0038). In silico analysis showed miR-7 binding site is conserved in mouse and human OIP5-AS1. However, human NANOG 3′-UTR lost the binding site for hsa-miR-7a-3. Therefore, we screened for other miRNAs that can be sponged by OIP5-AS1 and identified six potential miRNAs and their downstream target genes. Expression analysis showed downregulation of miRNAs and upregulation of downstream target genes, particularly in undifferentiated tumors with high-level of OIP5-AS1 suggesting OIP5-AS1 could post-transcriptionally modulate the downstream target genes. Further, systematic epigenomic analysis of OIP5-AS1 promoter revealed binding motifs for MYC, NANOG and KLF4 suggesting that OIP5-AS1 could be transactivated by stemness-associated transcription factors in cancer. OIP5-AS1 overexpression in undifferentiated oral tumors may be suggestive of enhanced cancer stemness, and consequently, poor clinical outcome. |
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