Publication: Targeting UCHL1 Induces Cell Cycle Arrest in High-Risk Multiple Myeloma with t(4;14)
Issued Date
2021-03-31
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ISSN
15322807
12194956
12194956
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2-s2.0-85104205857
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Mahidol University
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SCOPUS
Bibliographic Citation
Pathology and Oncology Research. Vol.27, (2021)
Suggested Citation
Parin Kamseng, Teerapong Siriboonpiputtana, Teeraya Puavilai, Suporn Chuncharunee, Karan Paisooksantivatana, Takol Chareonsirisuthigul, Mutita Junking, Wannasiri Chiraphapphaiboon, Pa Thai Yenchitsomanus, Budsaba Rerkamnuaychoke Targeting UCHL1 Induces Cell Cycle Arrest in High-Risk Multiple Myeloma with t(4;14). Pathology and Oncology Research. Vol.27, (2021). doi:10.3389/pore.2021.606567 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76240
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Title
Targeting UCHL1 Induces Cell Cycle Arrest in High-Risk Multiple Myeloma with t(4;14)
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Abstract
Multiple myeloma (MM) patients considered to be at high cytogenetic risk commonly fail to respond to standard treatment. A thorough understanding of the molecular mechanism of MM development is, therefore, needed. We endeavored to explore the transcriptional signature among different subgroups of newly diagnosed MM using gene chip-based expression microarray. Bone marrow samples of 15 newly diagnosed Thai MM patients were included. The chromosomal translocation t(4;14) was the most frequently identified genetic alteration in the high-risk subgroup. Cluster analysis from expression profiling demonstrated that high-risk MM have a distinctly different expression pattern compared to standard-risk patients. The most significant differentially expressed gene was UCHL1. Functional enrichment analysis by Gene Set Enrichment Analysis, FUNRICH, and Gene Ontology Panther pathway revealed the gene sets involved in cell cycle control to be enriched in the t(4;14) high-risk group. Interestingly, among the well-established downstream targets of UCHL1, only CCND2 was significantly expressed in the t(4;14) high-risk group. Suppression of UCHL1 protein level by LDN-5744 inhibitor could arrest the cell cycle in G1 phase in cell lines. These findings shed light on the molecular mechanism of UCHL1 in t(4;14) high-risk MM and support the evidence that alteration of the UCHL1 pathway may play a role in the pathogenesis of high-risk MM.