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Apigenin Targets MicroRNA-155, Enhances SHIP-1 Expression, and Augments Anti-Tumor Responses in Pancreatic Cancer.
Husain, Kazim; Villalobos-Ayala, Krystal; Laverde, Valentina; Vazquez, Oscar A; Miller, Bradley; Kazim, Samra; Blanck, George; Hibbs, Margaret L; Krystal, Gerald; Elhussin, Isra; Mori, Joakin; Yates, Clayton; Ghansah, Tomar.
Afiliación
  • Husain K; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Villalobos-Ayala K; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Laverde V; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Vazquez OA; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Miller B; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Kazim S; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Blanck G; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
  • Hibbs ML; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
  • Krystal G; Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne 3004, Australia.
  • Elhussin I; The Terry Fox Laboratory, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
  • Mori J; Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA.
  • Yates C; Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA.
  • Ghansah T; Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA.
Cancers (Basel) ; 14(15)2022 Jul 25.
Article en En | MEDLINE | ID: mdl-35892872
Pancreatic cancer (PC) is a deadly disease with a grim prognosis. Pancreatic tumor derived factors (TDF) contribute to the induction of an immunosuppressive tumor microenvironment (TME) that impedes the effectiveness of immunotherapy. PC-induced microRNA-155 (miRNA-155) represses expression of Src homology 2 (SH2) domain-containing Inositol 5'-phosphatase-1 (SHIP-1), a regulator of myeloid cell development and function, thus impacting anti-tumor immunity. We recently reported that the bioflavonoid apigenin (API) increased SHIP-1 expression which correlated with the expansion of tumoricidal macrophages (TAM) and improved anti-tumor immune responses in the TME of mice with PC. We now show that API transcriptionally regulates SHIP-1 expression via the suppression of miRNA-155, impacting anti-tumor immune responses in the bone marrow (BM) and TME of mice with PC. We discovered that API reduced miRNA-155 in the PC milieu, which induced SHIP-1 expression. This promoted the restoration of myelopoiesis and increased anti-tumor immune responses in the TME of heterotopic, orthotopic and transgenic SHIP-1 knockout preclinical mouse models of PC. Our results suggest that manipulating SHIP-1 through miR-155 may assist in augmenting anti-tumor immune responses and aid in the therapeutic intervention of PC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza