1. c-Myc inhibits LAPTM5 expression in B-cell lymphomas.
- Author
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Zhang, Yanqing, Zhang, Xin, Zhang, Yi, Xu, Han, Wei, Zichen, Wang, Xin, Li, Yan, Guo, Junrong, Wu, Fan, Fang, Xiao, Pang, Lei, Deng, Bin, and Yu, Duonan
- Subjects
GENE expression ,DIFFUSE large B-cell lymphomas ,LYMPHOMAS ,RITUXIMAB ,TRANSCRIPTION factors - 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]
- Published
- 2023
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