Knocking Down lncRNA HOXA-AS2 Mitigates the Progression of Epilepsy via Regulation of the miR-372-3p/STAT3 Axis.

AIM: The purposes of current research are to explore the potential activity of HOXA-AS2, a lncRNA (long non-coding RNA), in epilepsy progression, as well as the mechanisms behind its activity.

MATERIAL AND METHODS: Kainic acid (KA) was used to treat CTX-TNA2 cells (rat astroglial cells) as a cellular model of epilepsy. The qRT-PCR (quantitative reverse transcription-polymerase chain reaction) was conducted to examine the expressions levels of HOXA-AS2, miR-372-3p, as well as STAT3. Meanwhile, a combination of CCK (Cell Counting Kit)-8, flow cytometry and WB (Western-blot) were performed, in order to analyze cell viability and apoptosis, respectively. Further, the secretion levels of various inflammatory factors (IL-6, IL-1β, and TNF-α) were identified by ELISA. Besides, with the aim of validating the functional interaction between HOXA-AS2/STAT3 with miR‑372-3p, a reporter assay (dual-luciferase) was performed.

RESULTS: HOXA-AS2 and STAT3 expression levels were notably upregulated, whereas miR‑372-3p was downregulated in KA-treated CTX-TNA2 cells. Silencing HOXA-AS2 or overexpressing miR-372-3p inhibited the inflammatory factor secretions and cell apoptosis in KA-treated CTX-TNA2 cells. This study further showed that HOXA-AS2 negatively regulated miR‑372-3p, and miR‑372-3p targeted STAT3 mRNA. The suppression of miR-372-3p or excessive expression of STAT3 abrogated the rescue effect of si-HOXA-AS2 in KA-treated CTX-TNA2 cells.

CONCLUSION: Our study suggests that targeting HOXA-AS2 could alleviate cellular damages in the epileptic model by regulating miR-372-3p/STAT3 axis. Therefore, HOXA-AS2 might play the role of a potential anti-epilepsy therapeutic target.