Upregulation of microRNA-23b-3p induced by farnesoid X receptor regulates the proliferation and apoptosis of osteosarcoma cells

Abstract

Background: The downstream targets of farnesoid X receptor (FXR) such as miRNAs have a potent effect on the progression of many types of cancer. We aim to study the effects of FXR on osteosarcoma (OS) development and the potential role of microRNA-23b-3p. Methods: The expressions of FXR and miR-23b-3p in normal osteoblasts and five osteosarcoma cell lines were measured. Their correlations were analyzed by Pearson's test and verified by the introduction of FXR agonist, GW4064. TargetScan predicted that cyclin G1 (CCNG1) was a target for miR-23b-3p. The transfection of FXR siRNA was performed to confirm the correlation between FXR and miR-23b-3p. We further transfected miR-23b-3p inhibitor into MG-63 cells, and the transfected cells were treated with 5 μM GW4064 for 48 h. Quantitative PCR (qPCR) and Western blot were performed for expression analysis. Cell proliferation, cell apoptosis rate, and cell cycle distribution were assessed by clone formation assay and flow cytometry. Results: Scatter plot showed a positive correlation between FXR and miR-23b-3p (Pearson's coefficient test R 2 = 1.00, P = 0.0028). As CCNG1 is a target for miR-23b-3p, the treatment of GW4064 induced the downregulation of CCNG1 through upregulating miR-23b-3p. The inhibition of miR-23b-3p obviously promoted cell viability, proliferation, and cell cycle progression but reduced apoptosis rate of MG-63 cells; however, the treatment of GW4064 could partially reverse the effects of the inhibition of miR-23b-3p on OS cells. Conclusions: Upregulated FXR by GW4064 can obviously suppress OS cell development, and the suppressive effects may rely on miR-23b-3p/CCNG1 pathway.

Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer

“…However, it represents a significant cause of mortality in the world [ 196 ]. In a recent study, the low expression of FXR was reported in osteosarcoma cells [ 103 ]. However, activation of FXR by GW4064 was reported to increase miR-23b-3p, which lead to the suppression of cyclin G1 and cell proliferation and the inhibition of miR-23b-3p reverses this effect in MG-63 bone cancer cells.…”

“…However, activation of FXR by GW4064 was reported to increase miR-23b-3p, which lead to the suppression of cyclin G1 and cell proliferation and the inhibition of miR-23b-3p reverses this effect in MG-63 bone cancer cells. Therefore, the treatment with GW4064 increase miR-23b-3p and induce G1 phase cell cycle arrest by modulating the expressions of Bcl-2, Bax, and Caspase-3 that result in cell apoptosis [ 103 ]..…”

Epigenetics of ankylosing spondylitis: Recent developments

“…These include: (1) stability; (2) tissue specificity; (3) miRNA expression is related to specific physiological and pathological states; and (4) the ability of miRNA to differentiate, which can improve the accuracy of diagnosis 47 48 apoptosis, 49 differentiation 50 and development 51 . In recent years, with the deepening of research, the mechanism of ncRNA in complex diseases has become a research hotspot.…”

Long non-coding RNA KTN1-AS1 promotes progression in pancreatic cancer through regulating microRNA-23b-3p/high-mobility group box 2 axis

“…MiR-23b-3p induces suppressive function in various cancers. For instance, by targeting cyclin G1, it can regulate progression of osteosarcoma [ 11 ]. However, the relationship of KTN1-AS1 with miR-23b-3p in the modulation of PC development is still obscure.…”