Tumor suppressor function of miR-483-3p on squamous cell carcinomas due to its pro-apoptotic properties.
The frequent alteration of miRNA expression in many cancers, together with our recent reports showing a robust accumulation of miR-483-3p at the final stage of skin wound healing, and targeting of CDC25A leading to an arrest of keratinocyte proliferation, led us to hypothesize that miR-483-3p could also be endowed with antitumoral properties. We tested that hypothesis by documenting the in vitro and in vivo impacts of miR-483-3p in squamous cell carcinoma (SCC) cells. miR-483-3p sensitized SCC cells to serum deprivation- and drug-induced apoptosis, thus exerting potent tumor suppressor activities. Its pro-apoptotic activity was mediated by a direct targeting of several anti-apoptotic genes, such as API5, BIRC5, and RAN. Interestingly, an in vivo delivery of miR-483-3p into subcutaneous SCC xenografts significantly hampered tumor growth. This effect was explained by an inhibition of cell proliferation and an increase of apoptosis. This argues for its further use as an adjuvant in the many instances of cancers characterized by a downregulation of miR-483-3p.
CNRS UMR 7275, IPMC, Valbonne, France.
Thomas
T
Bertero
Isabelle
I
Bourget-Ponzio
Alexandre
A
Puissant
Agnès
A
Loubat
Bernard
B
Mari
Guerrino
G
Meneguzzi
Patrick
P
Auberger
Pascal
P
Barbry
Gilles
G
Ponzio
Roger
R
Rezzonico
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D015552:Injections, Intralesional; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin; D000077022:Survivin; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D047368:Tumor Burden / Q000235:genetics; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
C108386:API5 protein, human; D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C548912:MIRN483 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C120587:RAN protein, human; D000077022:Survivin; D020931:ran GTP-Binding Protein
apoptosis; epidermis; miR-483-3p; microRNA; tumor suppressor