LncRNA TSIX knockdown restores spinal cord injury repair through miR-30a/SOCS3 axis

ABSTRACT

Spinal cord injury (SCI) is a serious injury to the central nervous system. Previous studies have discovered that the development of SCI is associated with gene expression. The purpose of this study was to explore the significance of lncRNA TSIX in SCI and its underlying mechanism involved. An in vivo SCI mice model and an in vitro hypoxia-treated HT22 cells model were applied in this study. TSIX and SOCS3 expression in SCI tissues was measured by qRT-PCR, western blot and FISH assay. LV-sh-TSIX was injected into SCI mice intrathecally or subjected to HT22 cells to access the consequent alteration in inflammation response, cell apoptosis and functional recovery through ELISA, immunohistochemistry, TUNEL, flow cytometry assays and BMS scores. Then, the underlying mechanism of TSIX was analyzed by bioinformatics analysis and then confirmed by RIP, RNA pull-down and dual-luciferase reporter assay. It was identified that TSIX was up-regulated in HT22 cells under hypoxia operation and spinal cord tissues of SCI mice. TSIX knockdown improved the lesion size and BMS score and inhibited inflammation and cell apoptosis. MiR-30a was identified as a target for TSIX and SOCS3, and TSIX binds to miR-30a by competing with SOCS3, thereby counteracting miR-30a-mediated SOCS3 inhibition. In addition, LV-sh-TSIX effects were significantly overturned by miR-30a inhibition or SOCS3 over-expression. Knockdown of TSIX improved functional recovery and attenuated the inflammation response and cell apoptosis via miR-30a/SOCS3 axis. These results may provide a potential novel insight for SCI treatment.

KEYWORDS:

• TSIX
• inflammation
• apoptosis
• spinal cord injury

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work was supported by the Department of Education of Jiangxi Province [GJJ210152], and the Natural Science Foundation of Jiangxi Province [No. 20224BAB206033].

Notes on contributors

Zhimin Pan

Zhimin Pan, Yonsei University, Korea, spinal surgery, spinal cord clinical and scientific research work for more than 12 years.

Kai Huang

Kai Huang, Department of Orthopedics, Spine Surgery, Shanghai Second Medical University for nearly 20 years.

Nan Li

Nan Li, Peking University Health Science Center, Spine Surgery for 15 years.

Pingguo Duan

Pingguo Duan, Fudan University, Shanghai, orthopedics for 15 years. The spine is minimally invasive.

Jiang Huang

Jiang Huang, Department of Orthopedics, Jiangxi Medical College, 17 years.

Dong Yang

Dong Yang, Department of Orthopedics, Jiangxi Medical College, 20 years, Minimally invasive spinal cord injury research.

Zujue Cheng

Zujue Cheng, Jiangxi Medical College, Neurosurgery, spinal cord specialty for 5 years.

Yoon Ha

Yoon Ha, Yonsei University, South Korea, Neurospinal Surgery clinical and basic research for 22 years.

Jinsoo Oh

Jinsoo Oh, Yonsei University School of Medicine, South Korea, spinal cord injury research for 10 years.

Mengyun Yue

Mengyun Yue, Jiangxi Medical College, Surgical nursing for 4 years.

Xingen Zhu

Xingen Zhu, Neurosurgery Department, Jiangxi Medical College.

Da He

Da He, Peking University Health Science Center, has worked in spinal surgery for nearly 20 years.