SRY-box transcription factor 2 overlapping transcript (SOX2-OT) is a long noncoding RNA that is highly expressed in the serum of patients with pulmonary arterial hypertension (PAH), a new study published in Heart & Lung found.

SOX2-OT could therefore be a diagnostic biomarker for the disease, the authors said. Moreover, silencing SOX2-OT may attenuate hypoxia-induced proliferation, migration, antiapoptosis, and inflammation of pulmonary arterial smooth muscle cells and thereby prevent vascular remodeling and PAH progression.

It is already known that long noncoding RNAs, RNA molecules longer than 200 bp that do not code for proteins, are involved in the pathogenesis of PAH. Although their role in PAH is not clear, SOX2-OT is known to be upregulated in bladder cancer, glioblastoma, and cholangiocarcinoma.

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SOX2-OT has also been proposed as a diagnostic and prognostic marker for nonsmall cell lung cancer. Moreover, it has been shown to increase ischemic heart failure, regulate cardiomyocyte function, and aggravate hypoxia-induced cardiomyocyte injury in myocardial infarction. Finally, SOX2-OT prevents the treatment of pulmonary malignancies and worsens their clinical prognoses.

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Here, a team of researchers from China investigated the potential role of SOX2-OT in PAH. They first measured the serum levels of SOX2-OT in 82 patients with PAH and compared them to levels in 76 healthy volunteers.

They found that the levels of SOX2-OT in the serum of patients with PAH were significantly higher than that of the controls. “Elevated SOX2-OT levels significantly differentiated PAH patients from healthy controls, confirming high diagnostic feasibility,” the researchers wrote.

The team also found that SOX2-OT was increased in hypoxia-induced human pulmonary arterial smooth muscle cells grown in culture in a time-dependent manner and that silencing it could reverse these processes in the cells.

“Our experiments provide novel insight and therapeutic strategies for the treatment of PAH,” the researchers concluded.


Jiang Y, Hei B, Hao W, et al. Clinical value of lncRNA SOX2-OT in pulmonary arterial hypertension and its role in pulmonary artery smooth muscle cell proliferation, migration, apoptosis, and inflammatory. Heart Lung. Published online April 15, 2022. doi:10.1016/j.hrtlng.2022.04.002