Hsa_circ_0002060 Knockdown Ameliorates Osteoporosis by Targeting MiR-198-5p

Abstract

Osteoporosis (OP) is increasingly becoming one of a major health concerns all over the world. However, the limitations of current therapeutic drugs for OP are including considerable side effects and low efficacy. Therefore, it is required to develop new therapeutic drugs for OP. This study aimed to investigate the role of hsa_circ_0002060 in the regulation of osteoporosis.Osteoblast cells (hFOB 1.19) were transfected with hsa_circ_0002060 siRNA, following by stimulated with dexamethasone to mimic OP in vitro. Cell counting kit-8, apoptosis, and JC-1 mitochondrial membrane potential assays were used to evaluate the cell viability, apoptosis, and mitochondrial membrane potential, respectively. Western blot was conducted to detect the expression of proteins. In addition, the levels of reactive oxygen species, superoxide dismutase, glutathione and malondialdehyde were measured with ELISA. The putative target of hsa_circ_0002060 was verified by dual luciferase reporter assay and RNA pull down. At last, the role of hsa_circ_0002060 in the progression of OP was investigated with an ovariectomy (OVX)-induced OP mouse model. The results indicated DEX could induce cell viability decline in hFOB 1.19 cells, which was ameliorated by hsa_circ_0002060 knockdown. Consistently, DEX-induced cell apoptosis of hFOB 1.19 was ameliorated by hsa_circ_0002060 knockdown as well. As for the underlying mechanisms study, hsa_circ_0002060 was proved to regulate the viability of hFOB 1.19 cells through targeting miR-198-5p/Bax axis. Additionally, hsa_circ_0002060 knockdown alleviated ovariectomy-induced OP in a mouse model. Taken together, hsa_circ_0002060 knockdown alleviated the progression of OP by targeting miR-198-5p. Hsa_circ_0002060 might possibly be served as a therapeutic target for treating OP.

Comprehensive circRNA Analyses in Human Vertebrae of GIOP and Its Molecular Mechanism

“…We noticed that the expression of hsa_circ_0005778 was inconsistent with sequencing data; this may due to the limitation of sample size [ 25 ]. It has been reported that hsa_circ_0002060 depletion attenuates osteoporosis by regulating miR-198-5p[ 26 ]. circRNA_0006393 contributes to osteogenesis by targeting miR-145-5p/FOXO1 in glucocorticoid-induced osteoporosis [ 27 ].…”

The possible use of circRNAs as useful diagnostic, prognostic and therapeutic biomarkers in osteoporosis

“…circRNAs promoting OP circ_0002060 was also studied by Liu et al [25] .They tried to understand the function of this circRNA in the pathogenesis of OP, by studying its behaviour in osteoblast cells (hFOB 1. 19) treated with dexamethasone (DEX).…”

<i>Astragalus</i> Polysaccharide Suppresses Cell Proliferation and Invasion by Up-Regulation of miR-195-5p in Non-small Cell Lung Cancer

“…13) These small non-coding RNA molecules do not carry information about the structure of the protein but could regulate the gene expression by targeting selected mRNA that belong to the epigenetic mechanism. 14,15) MiRNAs, binding to untranslated region located in 3′ tail (3′-UTR) of mRNA, modulate its function through the impact on translation process, therefore miRNAs regulate gene expression post-transcriptionally. 16) In mammals, many researches have proved that miRNAs have important regulation functions in multidrug resistance (MDR) such as miR-125b, miR-491, miR-365, and miR-133a, [17][18][19][20] and several other miRNAs have been proved to be differentially expressed in sensitive and resistant lung cancer cells through next-generation sequencing in the miRNA database.…”