SOX2OT, the SOX2 overlapping transcript, is a long non-coding RNA. It is highly expressed in embryonic stem cells and is dynamically regulated during vertebrate embryogenesis, being delimited to the brain in adult mice and humans [5]. It has been implicated in multiple biological processes and diseases. Its mechanisms involve various factors and signaling pathways, and it may have both oncogenic and tumor-suppressor roles in different contexts [1].

In septic cardiomyopathy, knockdown of SOX2OT in mice recovered reduced cardiac function and improved mitochondrial membrane potential impaired by lipopolysaccharide (LPS), indicating it contributes to mitochondrial dysfunction via inhibiting SOX2 expression [3]. In esophageal squamous cell carcinoma (ESCC) tumorspheres, RNAi-mediated knockdown of SOX2OT suppressed stemness-related gene expression, sphere formation, and docetaxel resistance [2]. In heart failure, SOX2OT knockdown reduced myocardial injury and collagen deposition in HF mice, and it was found that SOX2OT promoted myocardial fibrosis by activating the TGF-β1/Smad3 pathway and formed a positive feedback loop with Smad3 [4].

In conclusion, SOX2OT plays crucial roles in processes like maintaining stem cell-like characteristics, mitochondrial function, and myocardial fibrosis. The gene knockout and related functional studies in mouse models have provided insights into its functions in diseases such as septic cardiomyopathy, ESCC, and heart failure, suggesting it could be a potential therapeutic target in these disease areas.