Silencing of lncRNA PKIA-AS1 Attenuates Spinal Nerve Ligation-Induced Neuropathic Pain Through Epigenetic Downregulation of CDK6 Expression

Jian-Zhong Hu; Jian-Zhong Hu; Zi-Jie Rong; Zi-Jie Rong; Miao Li; Miao Li; Ping Li; Ping Li; Ping Li; Li-Yuan Jiang; Li-Yuan Jiang; Zi-Xiang Luo; Zi-Xiang Luo; Chun-Yue Duan; Chun-Yue Duan; Yong Cao; Yong Cao; Hong-Bin Lu; Hong-Bin Lu

doi:10.3389/fncel.2019.00050

Frontiers in Cellular Neuroscience (Feb 2019)

Silencing of lncRNA PKIA-AS1 Attenuates Spinal Nerve Ligation-Induced Neuropathic Pain Through Epigenetic Downregulation of CDK6 Expression

Jian-Zhong Hu,
Jian-Zhong Hu,
Zi-Jie Rong,
Zi-Jie Rong,
Miao Li,
Miao Li,
Ping Li,
Ping Li,
Ping Li,
Li-Yuan Jiang,
Li-Yuan Jiang,
Zi-Xiang Luo,
Zi-Xiang Luo,
Chun-Yue Duan,
Chun-Yue Duan,
Yong Cao,
Yong Cao,
Hong-Bin Lu,
Hong-Bin Lu

Affiliations

Jian-Zhong Hu: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China
Jian-Zhong Hu: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Zi-Jie Rong: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China
Zi-Jie Rong: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Miao Li: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China
Miao Li: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Ping Li: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China
Ping Li: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Ping Li: Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, China
Li-Yuan Jiang: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China
Li-Yuan Jiang: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Zi-Xiang Luo: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China
Zi-Xiang Luo: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Chun-Yue Duan: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China
Chun-Yue Duan: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Yong Cao: Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China
Yong Cao: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Hong-Bin Lu: Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, China
Hong-Bin Lu: Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China

DOI: https://doi.org/10.3389/fncel.2019.00050
Journal volume & issue: Vol. 13

Abstract

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Neuropathic pain (NP) is among the most intractable comorbidities of spinal cord injury. Dysregulation of non-coding RNAs has also been implicated in the development of neuropathic pain. Here, we identified a novel lncRNA, PKIA-AS1, by using lncRNA array analysis in spinal cord tissue of spinal nerve ligation (SNL) model rats, and investigated the role of PKIA-AS1 in SNL-mediated neuropathic pain. We observed that PKIA-AS1 was significantly upregulated in SNL model rats and that PKIA-AS1 knockdown attenuated neuropathic pain progression. Alternatively, overexpression of PKIA-AS1 was sufficient to induce neuropathic pain-like symptoms in uninjured rats. We also found that PKIA-AS1 mediated SNL-induced neuropathic pain by directly regulating the expression and function of CDK6, which is essential for the initiation and maintenance of neuroinflammation and neuropathic pain. Therefore, our study identifies PKIA-AS1 as a novel therapeutic target for neuroinflammation related neuropathic pain.

Published in Frontiers in Cellular Neuroscience

ISSN: 1662-5102 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: http://www.frontiersin.org/cellular-neuroscience

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