Background: Lung cancer is one of the most common types of cancer and a leading cause of cancer-related deaths worldwide. Therefore, it is useful to know the biomarkers involved in the diagnosis and treatment of lung cancer.

Objectives: This study aimed to demonstration that the SOX2OT as a Long Non Coding RNA (LncRNAs), regulate gene expression through the molecular pathway of SOX2OT /miR194-5p/SOX5 axis in lung cancer.

Material and Methods: A549 cells transfected by SOX2OT-siRNA and the expression of SOX2OT and miR194-5p genes were studied by real time PCR befor and after transfection. Additionally the expression of the B-catenin, MMP9, P-STAT3, SOX5, VEGF proteins were investigated by western blotting, befor and after transfection.

Results: An increase in the expression of miR194-5p and a decrease in the expression of B-catenin, SOX5, P-STAT3, VEGF and MMP9 proteins was observed, after using SIRNA-SOXOT

Conclusions: According to the results of the present study, increasing SOX2OT in lung cancer seems to stimulate the expression of beta-catenin and thus supports the growth of lung cancer cells. On the other hand, , suggesting that SOX2OT increases the SOX5 transcription factor by sponging miRNA194-5P, and this molecule stimulates the expression of MMP9 and VEGF, the key molecules of metastasis and angiogenesis, by activating STAT3. Therefore, SOX2OT can be introduced as a poor prognosis marker in lung cancer and inhibiting SOX2OT can prevent the expression of key poor prognostic molecules, such as MMP9, VEGF, and beta-catenin in upstream.