Targeting of PFKFB3 with miR-206 but not mir-26b inhibits ovarian cancer cell proliferation and migration involving FAK downregulation.
Carcinoma, Ovarian Epithelial
/ genetics
Cell Line
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Down-Regulation
/ genetics
Female
Focal Adhesion Kinase 1
/ genetics
Gene Expression Regulation
/ genetics
Glycolysis
/ genetics
Human Umbilical Vein Endothelial Cells
Humans
MicroRNAs
/ genetics
Ovarian Neoplasms
/ genetics
Phosphofructokinase-2
/ genetics
FAK
PFKFB3
miR-206
miR-26b
ovarian cancer cells
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
02
12
2021
received:
29
07
2021
accepted:
20
12
2021
entrez:
2
2
2022
pubmed:
3
2
2022
medline:
15
2
2022
Statut:
ppublish
Résumé
Few studies explored the role of microRNAs (miRNAs) in the post-transcriptional regulation of glycolytic proteins and downstream effectors in ovarian cancer cells. We recently showed that the functional activation of the cytoskeletal regulator FAK in endothelial cells is fostered by the glycolytic enhancer 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). We tested the hypothesis that miR-206 and mir-26b, emerging onco-suppressors targeting PFKFB3 in estrogen-dependent tumors, would regulate proliferation and migration of serous epithelial ovarian cancer (EOC) cells via common glycolytic proteins, i.e., GLUT1 and PFKFB3, and downstream FAK. PFKFB3 was overexpressed in SKOV3, and its pharmacological inhibition with 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) significantly reduced cell proliferation and motility. Both miR-206 and miR-26b directly targeted PFKFB3 as evaluated by a luciferase reporter assay. However, endogenous levels of miR-26b were higher than those of miR-206, which was barely detectable in SKOV3 as well as OVCAR5 and CAOV3 cells. Accordingly, only the anti-miR-26b inhibitor concentration-dependently increased PFKFB3 levels. While miR-206 overexpression impaired proliferation and migration by downregulating PFKFB3 levels, the decreased PFKFB3 protein levels related to miR-26 overexpression had no functional consequences in all EOC cell lines. Finally, consistent with the migration outcome, exogenous miR-206 and miR-26b induced opposite effects on the levels of total FAK and of its phosphorylated form at Tyr576/577. 3PO did not prevent miR-26b-induced SKOV3 migration. Overall, these results support the inverse relation between endogenous miRNA levels and their tumor-suppressive effects and suggest that restoring miR-206 expression represents a potential dual anti-PFKFB3/FAK strategy to control ovarian cancer progression.
Identifiants
pubmed: 35107852
doi: 10.1096/fj.202101222R
doi:
Substances chimiques
MIRN206 microRNA, human
0
MIRN26A microRNA, human
0
MicroRNAs
0
PFKFB3 protein, human
EC 2.7.1.105
Phosphofructokinase-2
EC 2.7.1.105
Focal Adhesion Kinase 1
EC 2.7.10.2
PTK2 protein, human
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22140Informations de copyright
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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