The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth
Open accessAbstract
The LKB1 tumor suppressor gene is frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Loss of LKB1 promotes cancer progression and influences therapeutic responses in preclinical studies; however, specific targeted therapies for lung cancer with LKB1 inactivation are currently unavailable. Here, we have identified a long noncoding RNA (lncRNA) signature that is associated with the loss of LKB1 function. We discovered that LINC00473 is consistently the most highly induced gene in LKB1-inactivated human primary NSCLC samples and derived cell lines. Elevated LINC00473 expression correlated with poor prognosis, and sustained LINC00473 expression was required for the growth and survival of LKB1-inactivated NSCLC cells. Mechanistically, LINC00473 was induced by LKB1 inactivation and subsequent cyclic AMP-responsive element-binding protein (CREB)/CREB-regulated transcription coactivator (CRTC) activation. We determined that LINC00473 is a nuclear lncRNA and interacts with NONO, a component of the cAMP signaling pathway, thereby facilitating CRTC/CREB-mediated transcription. Collectively, our study demonstrates that LINC00473 expression potentially serves as a robust biomarker for tumor LKB1 functional status that can be integrated into clinical trials for patient selection and treatment evaluation, and implicates LINC00473 as a therapeutic target for LKB1-inactivated NSCLC.
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Metadata
- Authors
- Chen, Z., Li, J.-L., Lin, S., Cao, C., Gimbrone, N. T., Yang, R., Fu, D. A., Carper, M. B., Haura, E. B., Schabath, M. B., Lu, J., Amelio, A. L., Cress, W. D., Kaye, F. J., & Wu, L.
- Venue
- Journal of Clinical Investigation
- Published
- 2016-05-03
- Volume
- 126
- Issue
- 6
- Pages
- 2267-2279
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2345961903
- Cited by
- 194
- References
- 15
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chen, Z., Li, J.-L., Lin, S., Cao, C., Gimbrone, N. T., Yang, R., Fu, D. A., Carper, M. B., Haura, E. B., Schabath, M. B., Lu, J., Amelio, A. L., Cress, W. D., Kaye, F. J., & Wu, L. (2016). cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth. Journal of Clinical Investigation. https://doi.org/10.1172/jci85250
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