miR-550a-3p is a prognostic biomarker and exerts tumor-suppressive functions by targeting HSP90AA1 in diffuse malignant peritoneal mesothelioma.
Animals
Biomarkers
Cell Line, Tumor
Cell Movement
Cell Proliferation
/ genetics
Gene Expression Regulation, Neoplastic
HSP90 Heat-Shock Proteins
/ genetics
Humans
Lung Neoplasms
/ genetics
Male
Mesothelioma, Malignant
Mice
MicroRNAs
/ genetics
Peritoneal Neoplasms
/ genetics
Prognosis
RNA, Messenger
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
03
12
2021
accepted:
10
03
2022
pubmed:
31
3
2022
medline:
20
10
2022
entrez:
30
3
2022
Statut:
ppublish
Résumé
Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and rapidly lethal tumor, poorly responsive to conventional treatments. In this regards, the identification of molecular alterations underlying DMPM onset and progression might be exploited to develop novel therapeutic strategies. Here, we focused on miR-550a-3p, which we found downregulated in 45 DMPM clinical samples compared to normal tissues and whose expression levels were associated with patient outcome. Through a gain-of-function approach using miRNA mimics in 3 DMPM cell lines, we demonstrated the tumor-suppressive role of miR-550a-3p. Specifically, miRNA ectopic expression impaired cell proliferation and invasiveness, enhanced the apoptotic response, and reduced the growth of DMPM xenografts in mice. Antiproliferative and proapoptotic effects were also observed in prostate and ovarian cancer cell lines following miR-550a-3p ectopic expression. miR-550a-3p effects were mediated, at least in part, by the direct inhibition of HSP90AA1 and the consequent downregulation of its target proteins, the levels of which were rescued upon disruption of miRNA-HSP90AA1 mRNA pairing, partially abrogating miR-550a-3p-induced cellular effects. Our results show that miR-550a-3p reconstitution affects several tumor traits, thus suggesting this approach as a potential novel therapeutic strategy for DMPM.
Identifiants
pubmed: 35352023
doi: 10.1038/s41417-022-00460-7
pii: 10.1038/s41417-022-00460-7
pmc: PMC9576593
doi:
Substances chimiques
Biomarkers
0
HSP90 Heat-Shock Proteins
0
HSP90AA1 protein, human
0
MicroRNAs
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1394-1404Informations de copyright
© 2022. The Author(s).
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