Downregulation of miR-26 promotes invasion and metastasis via targeting interleukin-22 in cutaneous T-cell lymphoma.
Animals
Cell Line, Tumor
DNA-Binding Proteins
/ genetics
Down-Regulation
Gene Expression Regulation, Neoplastic
Humans
Interleukins
Lymphoma, T-Cell, Cutaneous
/ drug therapy
Mice
MicroRNAs
/ metabolism
RGS Proteins
/ genetics
Skin Neoplasms
/ pathology
Sorting Nexins
/ genetics
Transcription Factors
/ genetics
Interleukin-22
CTCL
IL-22
cutaneous T-cell lymphoma
interleukin-22
miR-26
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
revised:
25
01
2022
received:
02
11
2021
accepted:
02
02
2022
pubmed:
9
2
2022
medline:
12
4
2022
entrez:
8
2
2022
Statut:
ppublish
Résumé
It has been reported that certain microRNAs (miRNA) are associated with the pathogenesis of lymphoma. We have previously demonstrated that histone deacetylase inhibitors restore tumor-suppressive miRNAs, such as miR-16, miR-29, miR-150, and miR-26, in advanced cutaneous T-cell lymphoma (CTCL). Among these, the function of miR-26 remains unclear. In this study, we aimed to reveal the function of miR-26 in CTCL oncogenesis. First, we confirmed that the miR-26 family was markedly dysregulated in CTCL cell lines and primary samples. In vivo analysis using miR-26a-transduced CTCL cells injected into immunodeficient NOG mice demonstrated the significant prolonged survival of the mice, suggesting that the miRNA had a tumor-suppressive function. We performed gene expression assays and identified 12 candidate miR-26 targets, namely RGS13, FAM71F1, OAF, SNX21, CDH2, PTPLB, IL22, DNAJB5, CASZ1, CACNA1C, MYH10, and CNR1. Among these, IL22 was the most likely candidate target because the IL-22-STAT3-CCL20-CCR6 cascade is associated with tumor invasion and metastasis of advanced CTCL. In vitro analysis of IL22 and IL22RA knockdown and miR-26 transduction demonstrated inhibited CTCL cell migration. In particular, IL22 knockdown induced cell apoptosis. Finally, we conducted in vivo inoculation analysis of mice injected with shIL22-transfected CTCL cells, and found no tumor invasion or metastasis in the inoculated mice, although the control mice showed multiple tumor invasions and metastases. These results, along with our previous data, demonstrated that miR-26 is a tumor suppressor that is associated with tumor invasion and the metastasis of advanced CTCL by regulating the IL-22-STAT3-CCL20 cascade. Therefore, a IL-22-targeting therapy could be a novel therapeutic strategy for advanced CTCL.
Identifiants
pubmed: 35133054
doi: 10.1111/cas.15296
pmc: PMC8990290
doi:
Substances chimiques
CASZ1 protein, human
0
DNA-Binding Proteins
0
Interleukins
0
MIRN29 microRNA, mouse
0
MicroRNAs
0
Mirn26 microRNA, mouse
0
RGS Proteins
0
RGS13 protein, human
0
SNX21 protein, human
0
Sorting Nexins
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1208-1219Subventions
Organisme : JSPS KAKENHI
ID : 17K09914 (HT)
Organisme : The Japanese Society of Hematology Research Grant (SI)
Informations de copyright
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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