Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model
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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.
KeywordsBone cancer pain Hyperalgesia Circular RNA-9119 miR-26a TLR3
This work was supported by the Key Specialist Project of Clinical Medicine of Foshan City (Grant Number FSZDZK135049); Distinguished Youth Talent Fund Project of the First Medical Science Center of Foshan City in 2018; and Guangdong Medical Research Fund Project in 2019 (Grant Number A2019045). We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Compliance with Ethical Standards
This study was approved by the Committee on the Ethics of Animal Experiments of Shunde Hospital of Southern Medical University.
Conflict of Interest
The authors declare that they have no conflict of interest.
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