CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p/PIK3R1 axis

Mi, Bobin; Xiong, Yuan; Chen, Lang; Yan, Chenchen; Endo, Yori; Liu, Yi; Liu, Jing; Hu, Liangcong; Hu, Yiqiang; Sun, Yun; Cao, Faqi; Zhou, Wu; Liu, Guohui

doi:10.18632/aging.102524

Cited by 40 publications

(37 citation statements)

References 21 publications

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“…The activation of EIF2AK3 can in turn stimulate phosphorylation of EIF2A, leading to increased ATF4 expression, which plays a central role in osteoblast differentiation [32,33]. Indeed, several studies have previously demonstrated that BMP2 plays a regulatory role in various biological processes [34][35][36]. For example, one group found that a BMP activity gradient is essential for normal dorsoventral patterning during gastrulation [37].…”

Section: Discussionmentioning

confidence: 99%

The lncRNA Rhno1/miR-6979-5p/BMP2 Axis Modulates Osteoblast Differentiation

Xiong¹,

Chen²,

Yan³

et al. 2020

Int. J. Biol. Sci.

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The roles of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) as regulators of mRNA expression in various diseases have recently been reported. Osteoblast differentiation is the vital process which mediates bone formation and fracture healing. In present study, we found microRNA-6979-5p (miR-6979-5p) to be the most differentially expressed miRNA between normal bone and calluses of mice, and overexpression of miR-6979-5p was negatively associated with osteoblast differentiation. Through luciferase assays, we found evidence that bone morphogenetic protein 2 (BMP2) is a miR-6979-5p target gene that positively regulates osteoblast differentiation. We further identified the lncRNA Rhno1 as a competing endogenous RNA (ceRNA) of miR-6979-5p, and we verified that it was able to influence osteoblast differentiation both in vitro and in vivo. In summary, our data indicates that the lncRNA Rhno1/miR-6979-5p/BMP2 axis is a significant regulatory mechanism controlling osteoblast differentiation, and it may thus offer a novel therapeutic strategy for fracture healing.

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Section: Discussionmentioning

confidence: 99%

The lncRNA Rhno1/miR-6979-5p/BMP2 Axis Modulates Osteoblast Differentiation

Xiong¹,

Chen²,

Yan³

et al. 2020

Int. J. Biol. Sci.

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“…For example, Lang et al ( 22 ) provided evidence for the use of miR-25 to promote fracture healing by enhancing osteoblastic proliferation and differentiation through activation of the Wnt signaling pathway. Mi et al ( 23 ) demonstrated that decreased miR-7223-5p during fracture healing regulated osteoblastic proliferation and apoptosis by targeting PI3KR1, mediating the promoting effect of circRNA AFF4 on fracture healing. The expression of miR-203 in patients with fractures was also aberrant during healing and could inhibit the proliferation and promote the apoptosis of osteoblast cells by targeting prostate and breast cancer overexpressed 1( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Beneficial role of microRNA‑328‑3p in fracture healing by enhancing osteoblastic viability through the PTEN/PI3K/AKT pathway

Wang

Zhang

2020

Exp Ther Med

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Although fragility fracture is a global public health burden, the mechanisms underlying fracture healing remain unclear. The present study aimed to assess the dynamic expression pattern of microRNA-328-3p (miR-328-3p) during fracture healing in patients with fragility fracture and to explore the functional role and mechanisms of miR-328-3p in the regulation of osteoblastic viability. The expression levels of miR-328-3p was examined using reverse transcription-quantitative PCR (RT-qPCR). Osteoblastic proliferation and apoptosis were analyzed via MTT and flow cytometry assays. A luciferase reporter assay was adopted to confirm the interaction between miR-328-3p and its target gene PTEN, and western blotting was used to explore the activity of PI3K/AKT signaling. The results of the present study demonstrated that serum miR-328-3p expression did not significantly differ at the early stage of healing in patients with fracture, but was markedly decreased 14 and 21 days post fixation (P<0.01). PTEN was demonstrated to be a target gene of miR-328-3p and was inhibited by miR-328-3p overexpression in osteoblasts (P<0.001). miR-328-3p overexpression increased osteoblastic proliferation but decreased apoptotic rate, with these effects being reversed by PTEN overexpression (P<0.05). The expression of phosphorylated-AKT was elevated in osteoblasts by miR-328-3p overexpression, but this effect was abolished by overexpressing PTEN. Thus, the present study revealed that miR-328-3p may accelerate fracture healing by promoting osteoblastic viability through the PTEN/PI3K/AKT pathway.

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“…Moreover, in these cells, circRNA AFF4 silencing is shown to reduce Bcl-2 expression, an antiapoptotic protein, as well as PIK3R1. Furthermore, it showed circRNA AFF4 targeted miR-7223-5p, which inhibited PI3KR1, thus confirming circRNA AFF4 as a positive regulator of MC3T3-E1 proliferation (Mi et al, 2019). It is well known that reactive oxygen species (ROS) can kill bacteria as well as human cells.…”

Section: Circrna Involved In Osteoblast Regulationmentioning

confidence: 91%