NF-κB 1-induced LINC00665 regulates inflammation and apoptosis of neurons caused by spinal cord injury by targeting miR-34a-5p

ABSTRACT

Background: Spinal cord injury (SCI) has high disability rate and low cure rate, which frustrates the patients and brings a heavy burden to their families. This study aimed to explore whether NF-κB1 could induce the expression of LINC00665 and form a feedback loop with miR-34a-5p to regulate inflammation and apoptosis of neurons. Results: Basso, Beattie, and Bresnahan (BBB) scoring was decreased, damage for spinal cord tissue was aggravated and neuron number was decreased in SCI rats. The levels of TNF-α, IL-1β and IL-6 in serum and the expression of LINC00665 and NF-κB1 in spinal cord tissues were all increased in SCI rats. After LPS induction, PC12 cell viability was decreased. The expression of LINC00665 and NF-κB1 in LPS-induced PC12 cells was increased, which was partially reversed by BAY11-7082 (NF-κB inhibitor). Inhibition of LINC00665 improved cell viability, suppressed apoptosis and inflammation and down-regulated the NF-κB1 expression in LPS-induced PC12 cells. Furthermore, miR-34a-5p expression was decreased in LPS-induced PC12 cells, which could be promoted by inhibition of LINC00665. miR-34a-5p inhibitor restrained the effect of inhibition of LINC00665 on NF-κB1 expression in LPS-induced PC12 cells. Conclusion: inhibition of LINC00665 improved cell viability, suppressed apoptosis and inflammation in LPS-induced PC12 cells, and the NF-κB1/LINC00665/miR-34a-5ploop might be a useful therapeutic target in SCI treatment.

KEYWORDS:

• NFKB1
• LINC00665
• inflammation
• apoptosis
• spinal cord injury
• miR-34a-5p

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 81804185).

Notes on contributors

Qilong Deng

Qilong Deng, Doctor of medicine, attending physician, mainly engaged in clinical and basic research of spinal cord injury rehabilitation, presided over a national natural science fund, responsible for the design of undergraduate questions and fully participate in the implementation.

Lili Ma

Lili Ma, a resident physician, participated in many national and municipal projects, mainly responsible for cell culture and model construction.

Ting Chen

Ting Chen, Resident physician, mainly responsible for WB, PCR and other technical work.

Yu Yang

Yu Yang, orthopedics chief physician, presided and participated in a number of national and municipal projects, assisted Deng Qilong, Ma Lili, Chen Ting work.

Yuetao Ma

Yuetao Ma, medical doctor, chief physician, to provide project ideas and technical operation consulting services.

Lizhong Ma

Lizhong Ma, chief physician, head of rehabilitation medicine department, presided and participated in a number of national and provincial departmental level projects, responsible for the design and overall arrangement of this project.