Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53. / Fan, Kaiji; Spassova, Ivelina; Gravemeyer, Jan; Ritter, Cathrin; Horny, Kai; Lange, Anja; Gambichler, Thilo; Ødum, Niels; Schrama, David; Schadendorf, Dirk; Ugurel, Selma; Becker, Jürgen C.

In: Oncogene, Vol. 40, 2021, p. 980–996.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Fan, K, Spassova, I, Gravemeyer, J, Ritter, C, Horny, K, Lange, A, Gambichler, T, Ødum, N, Schrama, D, Schadendorf, D, Ugurel, S & Becker, JC 2021, 'Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53', Oncogene, vol. 40, pp. 980–996. https://doi.org/10.1038/s41388-020-01576-6

APA

Fan, K., Spassova, I., Gravemeyer, J., Ritter, C., Horny, K., Lange, A., Gambichler, T., Ødum, N., Schrama, D., Schadendorf, D., Ugurel, S., & Becker, J. C. (2021). Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53. Oncogene, 40, 980–996. https://doi.org/10.1038/s41388-020-01576-6

Vancouver

Fan K, Spassova I, Gravemeyer J, Ritter C, Horny K, Lange A et al. Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53. Oncogene. 2021;40:980–996. https://doi.org/10.1038/s41388-020-01576-6

Author

Fan, Kaiji ; Spassova, Ivelina ; Gravemeyer, Jan ; Ritter, Cathrin ; Horny, Kai ; Lange, Anja ; Gambichler, Thilo ; Ødum, Niels ; Schrama, David ; Schadendorf, Dirk ; Ugurel, Selma ; Becker, Jürgen C. / Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53. In: Oncogene. 2021 ; Vol. 40. pp. 980–996.

Bibtex

@article{98b9eaed7f154ffd9da3ecea72acfff7,
title = "Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53",
abstract = "Merkel cell carcinoma (MCC) is a highly invasive and metastatic skin cancer. While high expression of miR-375 is a characteristic of MCC, it seems not to contribute to the malignant phenotype of MCC cells. miR-375 enrichment in MCC-derived extracellular vesicles suggests its intercellular signaling function. Here, we demonstrate that horizontally transferred miR-375 causes fibroblast polarization toward cancer-associated fibroblasts (CAFs). The polarization is evidenced by phenotypic changes and induction of α-SMA, CXCL2, and IL-1β. Fibroblast polarization is inhibited by specific antagomirs and mimicked by experimental miR-375 expression. Mechanistically, miR-375 downregulates RBPJ and p53, two key players regulating fibroblast polarization. In clinical MCC samples, in situ hybridization located miR-375 in CAFs, which correlated with high α-SMA protein and low RBPJ and TP53 expression; single-cell RNAseq revealed a disparate fibroblast polarization negatively correlating with p53 pathway-related gene expression. Thus, the functional role of miR-375 in MCC is to generate a pro-tumorigenic microenvironment by inducing fibroblast polarization.",
author = "Kaiji Fan and Ivelina Spassova and Jan Gravemeyer and Cathrin Ritter and Kai Horny and Anja Lange and Thilo Gambichler and Niels {\O}dum and David Schrama and Dirk Schadendorf and Selma Ugurel and Becker, {J{\"u}rgen C.}",
year = "2021",
doi = "10.1038/s41388-020-01576-6",
language = "English",
volume = "40",
pages = "980–996",
journal = "Oncogene",
issn = "0950-9232",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Merkel cell carcinoma-derived exosome-shuttle miR-375 induces fibroblast polarization by inhibition of RBPJ and p53

AU - Fan, Kaiji

AU - Spassova, Ivelina

AU - Gravemeyer, Jan

AU - Ritter, Cathrin

AU - Horny, Kai

AU - Lange, Anja

AU - Gambichler, Thilo

AU - Ødum, Niels

AU - Schrama, David

AU - Schadendorf, Dirk

AU - Ugurel, Selma

AU - Becker, Jürgen C.

PY - 2021

Y1 - 2021

N2 - Merkel cell carcinoma (MCC) is a highly invasive and metastatic skin cancer. While high expression of miR-375 is a characteristic of MCC, it seems not to contribute to the malignant phenotype of MCC cells. miR-375 enrichment in MCC-derived extracellular vesicles suggests its intercellular signaling function. Here, we demonstrate that horizontally transferred miR-375 causes fibroblast polarization toward cancer-associated fibroblasts (CAFs). The polarization is evidenced by phenotypic changes and induction of α-SMA, CXCL2, and IL-1β. Fibroblast polarization is inhibited by specific antagomirs and mimicked by experimental miR-375 expression. Mechanistically, miR-375 downregulates RBPJ and p53, two key players regulating fibroblast polarization. In clinical MCC samples, in situ hybridization located miR-375 in CAFs, which correlated with high α-SMA protein and low RBPJ and TP53 expression; single-cell RNAseq revealed a disparate fibroblast polarization negatively correlating with p53 pathway-related gene expression. Thus, the functional role of miR-375 in MCC is to generate a pro-tumorigenic microenvironment by inducing fibroblast polarization.

AB - Merkel cell carcinoma (MCC) is a highly invasive and metastatic skin cancer. While high expression of miR-375 is a characteristic of MCC, it seems not to contribute to the malignant phenotype of MCC cells. miR-375 enrichment in MCC-derived extracellular vesicles suggests its intercellular signaling function. Here, we demonstrate that horizontally transferred miR-375 causes fibroblast polarization toward cancer-associated fibroblasts (CAFs). The polarization is evidenced by phenotypic changes and induction of α-SMA, CXCL2, and IL-1β. Fibroblast polarization is inhibited by specific antagomirs and mimicked by experimental miR-375 expression. Mechanistically, miR-375 downregulates RBPJ and p53, two key players regulating fibroblast polarization. In clinical MCC samples, in situ hybridization located miR-375 in CAFs, which correlated with high α-SMA protein and low RBPJ and TP53 expression; single-cell RNAseq revealed a disparate fibroblast polarization negatively correlating with p53 pathway-related gene expression. Thus, the functional role of miR-375 in MCC is to generate a pro-tumorigenic microenvironment by inducing fibroblast polarization.

U2 - 10.1038/s41388-020-01576-6

DO - 10.1038/s41388-020-01576-6

M3 - Journal article

C2 - 33311552

AN - SCOPUS:85097379123

VL - 40

SP - 980

EP - 996

JO - Oncogene

JF - Oncogene

SN - 0950-9232

ER -

ID: 254773626