LncRNA PSMB8-AS1 contributes to post-infarction heart failure by aggravating myocardial injury and inflammation.

Long non-coding RNA PSMB8-AS1 involvement in heart failure (HF) following acute myocardial infarction (AMI) remains unclear. This study aimed to investigate the clinical significance and potential mechanisms of PSMB8-AS1 in HF following AMI. This study enrolled 140 patients with HF following AMI and 130 AMI controls. An HF cell model was constructed by hypoxic treatment of H9C2 cardiomyocytes in vitro. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was employed to detect the target gene expression. Functional validation was conducted through cell counting kit-8 (CCK-8) assays, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). The biological functions and regulatory signalling pathways involved in the target genes of miR-574-5p were analyzed through bioinformatics. And the targeted relationship was validated using RNA immunoprecipitation (RIP) experiments and dual luciferase reporter assays. PSMB8-AS1 was highly expressed in the serum of patients with HF following AMI. PSMB8-AS1 showed potential as a risk stratification biomarker for HF in the post-AMI setting and was identified as an independent risk factor for this disease. In vitro cell experiments confirmed that PSMB8-AS1 was highly expressed in hypoxia-induced HF cells, and interfering with its expression could significantly reverse pathological phenotypes such as inhibition of cell proliferation, increased apoptosis, activation of inflammatory response, and oxidative damage. Mechanistically, PSMB8-AS1 specifically targeted miR-574-5p, while miR-574-5p targeted and suppressed SRY-box transcription factor 6 (SOX6). Simultaneous inhibition of PSMB8-AS1 and miR-574-5p expression partially attenuated the protective effect of PSMB8-AS1 interference. Subsequent silencing of SOX6 restored this protective effect, suggesting that the PSMB8-AS1/miR-574-5p/SOX6 regulatory axis participated in the pathological process of HF. PSMB8-AS1 promoted the development of HF following AMI by binding to miR-574-5p and upregulating SOX6 expression.