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Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma.
Zhao, Jie; Yang, Xuantao; Zhang, Haixi; Gu, Xuezhong.
Afiliación
  • Zhao J; Department of Hematology, The First People's Hospital of Yunnan Province, Yunnan Province Clinical Research Center for Hematologic Disease, Yunnan Province Clinical Center for Hematologic Disease, Kunming, 650032, China.
  • Yang X; Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, 650032, China.
  • Zhang H; Department of Hematology, The First People's Hospital of Yunnan Province, Yunnan Province Clinical Research Center for Hematologic Disease, Yunnan Province Clinical Center for Hematologic Disease, Kunming, 650032, China.
  • Gu X; Department of Hematology, The First People's Hospital of Yunnan Province, Yunnan Province Clinical Research Center for Hematologic Disease, Yunnan Province Clinical Center for Hematologic Disease, Kunming, 650032, China.
Oncol Res ; 32(2): 325-337, 2023.
Article en En | MEDLINE | ID: mdl-38186567
ABSTRACT
Multiple myeloma (MM) is a hematological tumor with high mortality and recurrence rate. Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM. However, the development of drug resistance is a pervasive obstacle to treating MM. Therefore, elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies. To elucidate the mechanisms of carfilzomib resistance, we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells. Differential gene expression analyses revealed major alterations in the major histocompatibility complex (MHC) and cell adhesion molecules. The upregulation of the tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) gene was accompanied by the downregulation of MHC genes and cell adhesion molecules. Furthermore, to investigate the roles of these genes, we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules. Furthermore, TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice, indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity. Furthermore, our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules. The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity. Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mieloma Múltiple Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Oncol Res Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mieloma Múltiple Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Oncol Res Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos