lncRNA PRR34-AS1 knockdown represses neuroinflammation and neuronal death in traumatic brain injury by inhibiting microRNA-498 expression

ABSTRACT

Objective

Traumatic brain injury (TBI) can result in motor and cognitive dysfunction and is a possible risk factor for the subsequent development of dementia. However, the pathogenesis of TBI remains largely unclear. This study investigated the roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in inflammation and neuronal apoptosis following TBI.

Methods

The lncRNA expression profiles in the cerebral cortices of TBI model mice and sham-operated mice were analyzed using microarray. We focused on an upregulated lncRNA, PRR34-AS1, because of its known modulatory role in apoptosis and inflammation.

Results

Our findings indicated that the knockdown of PRR34-AS1 inhibited inflammation and neuronal apoptosis and improved long-term neurological function. Using an in vitro, cell-based model of etoposide-induced primary cortical neuronal injury, we demonstrated that PRR34-AS1 levels were higher in injured model cells than in untreated control cells. Silencing of PRR34-AS1 suppressed etoposide-induced apoptosis and the production of inflammatory mediators in primary cortical neurons. PRR34-AS1 directly targets microRNA-498 (miR-498) in primary cortical neurons. Importantly, the inhibition of miR-498 expression counteracted the effects of PRR34-AS1 silencing on neuronal apoptosis and inflammation.

Conclusions

These findings indicate that PRR34-AS1 may be a useful therapeutic target for TBI.

KEYWORDS:

• TBI
• neurological function
• primary cortical neurons
• PRR34-AS1
• MiR-498
• apoptosis
• inflammation

Acknowledgments

Not applicable

Disclosure Statement

No potential conflict of interest was reported by the authors.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/02699052.2023.2192524.

Additional information

Funding

This work was supported by the Horizontal Subject: Study on the Mechanism of Bone Marrow Mesenchymal Stem cells promoting Angiogenesis related factors in Acute Cerebral Infarction [grant number 20201125033] and Horizontal Subject: Study on the Mechanism of Sequential treatment of Butylphthalide in promoting Angiogenesis related factors in Acute Cerebral Infarction [grant number 20180416061]