期刊
ONCOGENE
卷 34, 期 39, 页码 5046-5054出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2014.424
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资金
- Ligue contre le Cancer (equipe labelisee)
- Agence National de la Recherche (ANR)
- Association pour la recherche sur le cancer (ARC)
- Canceropole Ile-de-France
- AXA Chair for Longevity Research
- Institut National du Cancer (INCa)
- Fondation Bettencourt-Schueller
- Fondation de France
- Fondation pour la Recherche Medicale (FRM)
- European Commission (ArtForce)
- European Research Council (ERC)
- LabEx Immuno-Oncology
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Paris Alliance of Cancer Research Institutes (PACRI)
- German Ministry of education and research through the Alexander von Humboldt Foundation Sofja Kovalevskaja Award
A subset of promoters bidirectionally expresses long non-coding RNAs (ncRNAs) of unknown function and protein-coding genes (PCGs) in parallel. Here, we define a set of 1107 highly conserved human bidirectional promoters that mediate the linked expression of long ncRNAs and PCGs. Depletion of the long ncRNA expressed from the RB1 promoter, ncRNA-RB1, reveals regulatory effects different from the RB1-controlled transcriptional program. ncRNA-RB1 positively regulates the expression of calreticulin (CALR) that in response to certain therapeutic interventions can translocate from the endoplasmic reticulum to the cell surface, hence activating anticancer immune responses. Knockdown of ncRNA-RB1 in tumor cells reduced expression of CALR, impaired the translocation of the protein to the cell surface upon treatment with anthracylines and consequently inhibited the cellular uptake by macrophages. In conclusion, co-transcription of ncRNA-RB1 and RB1 provides a positive link between the expression of the two tumor suppressors RB1 and the immune-relevant CALR protein. This regulatory interplay exemplifies disease-relevant co-regulation of two distinct gene products, in which loss of expression of one oncosuppressor protein entails the abolition of additional tumor-inhibitory mechanisms.
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