circStrn3 is involved in bone cancer pain regulation in a rat model

Zhang, Yiwen; Zhang, Xiaoxia; Xing, Zumin; Tang, Shanjiang; Chen, Hanwen; Zhang, Zhongqi; Li, Jiyuan; Li, Yalan

doi:10.1093/abbs/gmaa018

Cited by 12 publications

(11 citation statements)

References 63 publications

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“…The BCP model was established according to the method previously reported ( Zhou et al, 2015 ; Hu et al, 2019 ; Shenoy et al, 2019 ; Zhang et al, 2020 ). In detail, the young rat was intraperitoneally injected with 2 × 10 7 Walker 256 cells.…”

Section: Methodsmentioning

confidence: 99%

Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression

Qian

Zhou

et al. 2021

Front. Pharmacol.

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Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (**p < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (**p < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (**p < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (**p < 0.01 vs. BCP + NS). What’s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.

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Section: Methodsmentioning

confidence: 99%

Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression

Qian

Zhou

et al. 2021

Front. Pharmacol.

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“…Li et al found that circStrn3 might be a potential biomarker for bone cancer pain through regulating cancer cell apoptosis and proliferation. 17 Chen et al found that the knockdown of circStrn3 effectively inhibited cell proliferation and promoted epithelial mesenchymal transition in glomerular mesangial cells. 18 Furthermore, Thum et al con rmed that circStrn3 was regulated on doxorubicin treatment in the heart.…”

Section: Discussionmentioning

confidence: 99%

CircStrn3 Targeting microRNA-9-5p is Involved in the Regulation of Cartilage Degeneration and Subchondral Bone Remodeling in Osteoarthritis

Ding

Chen

et al. 2021

SSRN Journal

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Background: Osteoarthritis (OA) is the most frequent chronic degenerative joint disease, which is a "whole joint" disease including the pathological changes in the cartilage, subchondral bone and the synovium. Mechanical instability is the initiation of the development of OA.Methods: Minus RNA sequencing, uorescence in situ hybridization and quantitative real-time PCR were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes.Stimulate chondrocytes to secrete exosomes miR-9-5p by stretching strain. Intra-articular injection of exosomes miR-9-5p into the OA model induced by the operation of instability of the medial meniscus in mice.Results: In the present study, minus RNA sequencing data showed that tensile strain could decrease the expression of circStrn3 in chondrocytes. The results of uorescence in situ hybridization and quantitative Real-time PCR showed that circStrn3 expression was signi cantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively 'sponging' miRNA-9-5p targeting kruppel-like factor 5 (KLF5), indicating that the decreasing of circStrn3 might be a protective factor in mechanical instability-induced OA. Further studies showed that the tensile strain stimulated chondrocytes to secrete exosomes miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblasts differentiation by targeting KLF5. In addition, intra-articular injection of exosomal miR-9-5p obviously alleviated the progression of OA induced by destabilized medial meniscus surgery in mice.Conclusions: Taken together, these results demonstrated that the reduction of circStrn3 caused the increasing of miR-9-5p, which acted as a protective factor in mechanical instability-induced OA and provided a novel mechanism of communication among joint components and a potential application for the treatment of OA.

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“…In our previous study, we successfully created BCP rat models [20]. In this study, the existence of circRNAs in the bone marrow tissues of rat BCP models was characterized by both Sanger sequencing and RT-PCR combined with agarose gel electrophoresis.…”

Section: Circular Rna Characterizationmentioning

confidence: 99%

The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

et al. 2021

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Treatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

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circStrn3 is involved in bone cancer pain regulation in a rat model

Cited by 12 publications

References 63 publications

Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression

Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression

CircStrn3 Targeting microRNA-9-5p is Involved in the Regulation of Cartilage Degeneration and Subchondral Bone Remodeling in Osteoarthritis

The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

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