Chongqing Medical University, Chongqing, 400016, China; Department of Medical Imaging, Inner Mongolia People's Hospital, Hohhot, 010017, China.
Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Biochem Biophys Res Commun. 2018 Nov 2;505(3):644-650. doi: 10.1016/j.bbrc.2018.09.158. Epub 2018 Oct 2.
Neuropathic pain is one of the most common diabetic complications and significantly decrease the quality of life. The aetiology of the painful diabetic neuropathic pain is not fully clear. Circular RNAs (circRNAs) have been identified as miRNA sponges and involved in various biological processes, including pain. CircHIPK3 is a circRNA that have been shown to be an oncogene or tumor suppressor to regulate cancer cells growth by sponging multiple miRNAs. However, the role of circHIPK3 in diabetic neuropathic pain remains unknown. The aim of the present study was to elucidate the possible role of circHIPK3 in the control of diabetic neuropathic pain. We found that circHIPK3 are highly abundant in serum from diabetes patients who suffered from neuropathic pain and in dorsal root ganglion from STZ-induced diabetes rats. Upregulation of circHIPK3 was positively associated with grade neuropathic pain in patients with type 2 diabetes. Silencing circHIPK3 alleviated neuropathic pain in diabetic rats, which was involved in neuroinflammation. Further mechanistic investigation demonstrated that circHIPK3 interacted with miR-124 and negatively regulated its expression. MiR-124 inhibitor can reverse circHIPK3 knockdown-mediated alleviation of neuropathic pain and inhibition of neuroinflammation in diabetic rats. We present the first evidence that intrathecal circHIPK3 shRNA treatment can be used to treat neuropathic pain of diabetic rats.
神经病理性疼痛是最常见的糖尿病并发症之一,显著降低了生活质量。痛性糖尿病性神经病理性疼痛的病因尚不完全清楚。环状 RNA(circRNAs)已被鉴定为 miRNA 海绵,并参与包括疼痛在内的各种生物学过程。CircHIPK3 是一种 circRNA,已被证明通过海绵吸附多种 miRNA 来调节癌细胞生长,发挥癌基因或肿瘤抑制基因的作用。然而,circHIPK3 在糖尿病性神经病理性疼痛中的作用尚不清楚。本研究旨在阐明 circHIPK3 在控制糖尿病性神经病理性疼痛中的可能作用。我们发现,患有神经病理性疼痛的糖尿病患者血清中和 STZ 诱导的糖尿病大鼠背根神经节中 circHIPK3 含量丰富。circHIPK3 的上调与 2 型糖尿病患者神经病变疼痛的严重程度呈正相关。沉默 circHIPK3 可减轻糖尿病大鼠的神经病理性疼痛,这与神经炎症有关。进一步的机制研究表明,circHIPK3 与 miR-124 相互作用并负调控其表达。miR-124 抑制剂可逆转 circHIPK3 敲低介导的糖尿病大鼠神经病理性疼痛减轻和神经炎症抑制。我们首次证明鞘内注射 circHIPK3 shRNA 治疗可用于治疗糖尿病大鼠的神经病理性疼痛。