Article ; Online: Long noncoding RNA ELDR promotes cell cycle progression in normal oral keratinocytes through induction of a CTCF-FOXM1-AURKA signaling axis.
The Journal of biological chemistry
2022 Volume 298, Issue 5, Page(s) 101895
Abstract: Long noncoding RNAs (lncRNAs) have gained widespread attention as a new layer of regulation in biological processes during development and disease. The lncRNA ELDR (EGFR long noncoding downstream RNA) was recently shown to be highly expressed in oral ... ...
| Abstract | Long noncoding RNAs (lncRNAs) have gained widespread attention as a new layer of regulation in biological processes during development and disease. The lncRNA ELDR (EGFR long noncoding downstream RNA) was recently shown to be highly expressed in oral cancers as compared to adjacent nontumor tissue, and we previously reported that ELDR may be an oncogene as inhibition of ELDR reduces tumor growth in oral cancer models. Furthermore, overexpression of ELDR induces proliferation and colony formation in normal oral keratinocytes (NOKs). In this study, we examined in further detail how ELDR drives the neoplastic transformation of normal keratinocytes. We performed RNA-seq analysis on NOKs stably expressing ELDR (NOK-ELDR), which revealed that ELDR enhances the expression of cell cycle-related genes. Expression of Aurora kinase A and its downstream targets Polo-like kinase 1, cell division cycle 25C, cyclin-dependent kinase 1, and cyclin B1 (CCNB1) are significantly increased in NOK-ELDR cells, suggesting induction of G2/M progression. We further identified CCCTC-binding factor (CTCF) as a binding partner of ELDR in NOK-ELDR cells. We show that ELDR stabilizes CTCF and increases its expression. Finally, we demonstrate the ELDR-CTCF axis upregulates transcription factor Forkhead box M1, which induces Aurora kinase A expression and downstream G2/M transition. These findings provide mechanistic insights into the role of the lncRNA ELDR as a potential driver of oral cancer during neoplastic transformation of normal keratinocytes. |
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| MeSH term(s) | Aurora Kinase A/metabolism ; Biological Phenomena ; Cell Division ; Cell Line, Tumor ; Cell Proliferation/genetics ; Forkhead Box Protein M1/genetics ; Forkhead Box Protein M1/metabolism ; Forkhead Transcription Factors/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Keratinocytes/metabolism ; Mouth Neoplasms/genetics ; Mouth Neoplasms/pathology ; RNA, Long Noncoding/genetics |
| Chemical Substances | FOXM1 protein, human ; Forkhead Box Protein M1 ; Forkhead Transcription Factors ; RNA, Long Noncoding ; AURKA protein, human (EC 2.7.11.1) ; Aurora Kinase A (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2022-04-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2997-x |
| ISSN | 1083-351X ; 0021-9258 |
| ISSN (online) | 1083-351X |
| ISSN | 0021-9258 |
| DOI | 10.1016/j.jbc.2022.101895 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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