Knockdown of hsa_circ_0001275 reverses dexamethasone-induced osteoblast growth inhibition via mediation of miR-377/CDKN1B axis

Abstract

Background Osteoporosis affects the quality of life among middle-aged and elderly individuals. In addition, dysfunction of osteoblasts can lead to the progression of osteoporosis. Circular (circ)RNAs are involved in various types of diseases, including osteoporosis. Moreover, it has been reported that hsa_circ_0001275 expression is upregulated in osteoporosis. However, the effects of hsa_circ_0001275 on the growth of osteoblasts remain unclear. Methods In the present study, the gene and protein expression levels in hFOB1.19 cells were detected via reverse transcription-quantitative (RT-qPCR) and western blot analyses, respectively. In addition, alkaline phosphatase (ALP) activity and calcium nodules were examined by ALP and alizarin red staining, respectively. Cell proliferation was measured using the Cell Counting Kit-8 assay. Cell apoptosis and cell cycle were analyzed by flow cytometry. Furthermore, dual luciferase reporter and RNA pull-down assay were used to confirm the association among hsa_circ_0001275, microRNA (miR)-377 and CDKN1B. Results DEX-induced hFOB1.19 cell growth inhibition was significantly reversed by silencing hsa_circ_0001275. Moreover, DEX significantly increased ALP activity and calcium nodules in hFOB1.19 cells, while this effect was significantly reversed in the presence of hsa_circ_0001275 small interfering RNA. In addition, miR-377 was sponged by hsa_circ_0001275 and CDKN1B was directly targeted by miR-377 in hFOB1.19 cells. Furthermore, the therapeutic effect of hsa_circ_0001275 knockdown on osteoporosis was notably reversed by miR-377 antagomir. Conclusion The data demonstrated that knockdown of hsa_circ_0001275 reversed DEX-induced osteoblast growth inhibition via activation of the miR-377/CDKN1B axis. Therefore, this study might shed new lights on the treatment of osteoporosis.

LncRNA AC006064.4–201 serves as a novel molecular marker in alleviating cartilage senescence and protecting against osteoarthritis by destabilizing CDKN1B mRNA via interacting with PTBP1

“…And the results further revealed that PTBP1 was able to bind to the mRNA of CDKN1B and improve its stability, resulting in the increased translation of CDKN1B protein. Mounting evidence suggested that CDKN1B is a key regulator of cell cycle progression, which was recognized as an important senescence marker in aging-related diseases such as osteoporosis [ 49 , 50 ], atherosclerosis [ 51 ] and Alzheimer’s disease [ 52 ]. In the present study, we performed functional experiments and reported that CDKN1B is positively correlated with chondrocyte senescence and OA progression.…”

hsa_circ_0001275 Is One of a Number of circRNAs Dysregulated in Enzalutamide Resistant Prostate Cancer and Confers Enzalutamide Resistance In Vitro

“…Studies have shown a historical role of miRNA “sponging” in circRNA-miRNA–mRNA networks as playing important roles in both gene regulation and carcinogenesis [ 25 ]. For example, Xu et al recently showed that dexamethasone-induced osteoblast growth inhibition can be reversed by downregulating hsa_circ_0001275 which mediated the miR-377/CDKN1B axis in an effort to discover new treatment for osteoporosis [ 46 ]. Furthermore, Formosa et al previously demonstrated a role for miR-377 as a tumour suppressor miRNA targeting FZD4, a gene involved in epithelial-to-mesenchymal transition in prostate cancer [ 47 ].…”

Long non-coding RNA Homeobox D gene cluster antisense growth-associated long noncoding RNA/microRNA-182-5p/Homeobox protein A10 alleviates postmenopausal osteoporosis via accelerating osteoblast differentiation of bone marrow mesenchymal stem cells

“…Then, cells were treated with propanol (15 min), incubation solution (6 h), cobalt nitrate (15 min), and ammonium sulfide (5 min) (all 200 μL). Optical density at 490 nm was read on a microplate reader (Varioskan LUX; Thermo Fisher Scientific) [ 30 ].…”