1. LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors.
- Author
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Arunkumar G, Anand S, Raksha P, Dhamodharan S, Prasanna Srinivasa Rao H, Subbiah S, Murugan AK, and Munirajan AK
- Subjects
- Adult, Base Sequence, Binding Sites, Carcinoma genetics, Carcinoma pathology, Cell Line, Tumor, Female, Humans, Kruppel-Like Factor 4, Male, MicroRNAs genetics, Middle Aged, Models, Biological, Mouth Neoplasms mortality, Neoplasm Grading, Neoplasm Invasiveness, Neoplasm Staging, Neoplastic Stem Cells pathology, Prognosis, RNA Interference, Transcription Factors, Gene Expression Regulation, Neoplastic, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Neoplastic Stem Cells metabolism, RNA, Long Noncoding genetics
- 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.
- Published
- 2018
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