RETRACTED ARTICLE: Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain M
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Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model Zhongqi Zhang 1 & Xiaoxia Zhang 1 & Yanjing Zhang 1 & Jiyuan Li 1 & Zumin Xing 1
&
Yiwen Zhang 1
Received: 18 March 2019 / Accepted: 9 July 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Altered expression of circular RNA (circRNA) is recognized as a contributor to malignant pain where microRNA (miRNA) exerts an essential effect. We generated a murine model for bone malignancy pain in which 2472 osteolytic sarcoma cells were injected into the femurs of mice. CircRNA microarray and quantitative PCR (qPCR) and revealed that circ9119 expression was repressed in the spinal cord of bone malignancy pain model mice, which is the first relay site involved in the transmission of nociceptive information to the cerebrum of mice that receive spinal analgesics for malignancy pain. Overexpression of circ9119 by plasmid injection in the model mice reduced progressive thermal hyperalgesia and mechanical hyperalgesia. Bioinformatics prediction and dual-luciferase reporter assay showed that circ9119 functions as a sponge of miR-26a, which targets the TLR3 3′untranslated region. Furthermore, expression of miR-26a was elevated and TLR3 level was repressed in bone malignancy pain model mice, which were counteracted by circ9119 in the spinal cord of tumor-bearing mice. Moreover, excessive expression of miR-26a was involved in the recovery of mice from progressive thermal hyperalgesia and mechanical hyperalgesia triggered via circ9119. TLR3 knockdown in bone malignancy pain model mice thoroughly impaired pain in the initial stages and reduced the effects of circ9119 on hyperalgesia. Our research findings indicate that targeting the circ9119-miR-26a-TLR3 axis may be a promising analgesic strategy to manage malignancy pain. Keywords Bone cancer pain . Hyperalgesia . Circular RNA-9119 . miR-26a . TLR3
Introduction
Zhongqi Zhang and Xiaoxia Zhang contributed equally to this work. * Zumin Xing [email protected] * Yiwen Zhang [email protected] Zhongqi Zhang [email protected] Xiaoxia Zhang [email protected] Yanjing Zhang [email protected] Jiyuan Li [email protected] 1
Department of Anesthesiology, Shunde Hospital of Southern Medical University, No. 1 Lunjiaojiazi Road, Shunde District, Foshan 528308, Guangdong, China
Patients experiencing malignancies with bone metastasis usually have a low quality of life. Bone complications caused by metastasis are found in 70% of patients with terminal prostate or breast cancer (Coleman 1997; Coyle et al. 1990; Mercadante 1997; Portenoy and Lesage 1999), and metastasis is considered as the dominant contributor to malignancyinduced bone pain. Mechanical allodynia refers to the painful sensation caused by non-noxious mechanical triggers. In patients with bone malignancies, acute pain provoked by movement may arise from mild limb movement, turning in bed, and coughing. It also has impaired responses to traditional treatment. Circular RNA (circRNA) is a t
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