Inauhzin(c) Inactivates c-Myc Independently of p53
| Autor: | Jun-Ming Liao, Shelya Zeng, Sung-Hoon Kim, Daniel Nguyen, Qian Hao, Bo Cao, Xiang Zhou, Ji Hoon Jung, Hua Lu, Qi Zhang |
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| Rok vydání: | 2015 |
| Předmět: |
Ribosomal Proteins
Cancer Research Indoles Apoptosis Biology Proto-Oncogene Proteins c-myc Phenothiazines microRNA Humans RNA Messenger Cell Proliferation Pharmacology Gene knockdown Gene Expression Regulation Leukemic Cell growth Burkitt Lymphoma Molecular biology Raji cell Oncology Argonaute Proteins Cancer cell Molecular Medicine Oncogene MYC Tumor Suppressor Protein p53 Signal transduction Signal Transduction Research Paper |
| Zdroj: | Cancer Biology & Therapy. 16:412-419 |
| ISSN: | 1555-8576 1538-4047 |
| Popis: | Oncogene MYC is deregulated in many human cancers, especially in lymphoma. Previously, we showed that inauhzin (INZ) activates p53 and inhibits tumor growth. However, whether INZ could suppress cancer cell growth independently of p53 activity is still elusive. Here, we report that INZ(c), a second generation of INZ, suppresses c-Myc activity and thus inhibits growth of human lymphoma cells in a p53-independent manner. INZ(c) treatment decreased c-Myc expression at both mRNA and protein level, and suppressed c-Myc transcriptional activity in human Burkitt's lymphoma Raji cells with mutant p53. Also, we showed that overexpressing ectopic c-Myc rescues the inhibition of cell proliferation by INZ(c) in Raji cells, implicating c-Myc activity is targeted by INZ(c). Interestingly, the effect of INZ(c) on c-Myc expression was impaired by disrupting the targeting of c-Myc mRNA by miRNAs via knockdown of ribosomal protein (RP) L5, RPL11, or Ago2, a subunit of RISC complex, indicating that INZ(c) targets c-Myc via miRNA pathways. These results reveal a new mechanism that INZ(c) targets c-Myc activity in human lymphoma cells. |
| Databáze: | OpenAIRE |
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