Back to Search
Start Over
c-Myc inhibits LAPTM5 expression in B-cell lymphomas.
- Source :
-
Annals of Hematology . Dec2023, Vol. 102 Issue 12, p3499-3513. 15p. - Publication Year :
- 2023
-
Abstract
- Myc is a pivotal protooncogenic transcription factor that contributes to the development of almost all Burkitt's lymphomas and about one-third of diffuse large B-cell lymphomas. How B-cells sustain their uncontrolled proliferation due to high Myc is not yet well defined. Here, we found that Myc trans-represses the expression of murine LAPTM5, a gene coding a lysosome-associated protein, by binding to two E-boxes in the LAPTM5 promoter. While the product of intact mRNA (CDS+3′UTR) of LAPTM5 failed to suppress the growth of B-lymphomas, either the protein coded by coding sequence (CDS) itself or the non-coding 3′-untranslated region (3′UTR) mRNA was able to inhibit the growth of B-lymphomas. Moreover, Myc trans-activated miR-17-3p, which promoted tumor growth. Strikingly, LAPTM5 3′UTR contains 11 miR-17-3p-binding sites through which the LAPTM5 protein synthesis was inhibited. The functional interplay between low LAPTM5 mRNA and high miR-17-3p due to high Myc in B-lymphomas leads to further dampening of tumor-suppressive LAPTM5 protein, which promotes tumor progression. Our results indicate that Myc inhibits LAPTM5 expression in B-lymphoma cells by transcriptional and post-transcriptional modifications. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09395555
- Volume :
- 102
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Annals of Hematology
- Publication Type :
- Academic Journal
- Accession number :
- 173556813
- Full Text :
- https://doi.org/10.1007/s00277-023-05434-9