LncRNA NBR2 Regulates Cancer Cell Stemness and Predicts Survival in Non-small Cell Cancer Patients by Downregulating TGF-ß1.

BACKGROUND: LncRNA NBR2 is a key regulator in cancer metabolism. However, its role in lung cancer is unknown. OBJECTIVE: This study aimed to explore the function of NBR2 in non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. METHODS: Paired NSCLC and non-cancer tissues were collected from 68 patients with NSCLC. The expression of NBR2 and transforming growth factor-ß1 (TGF-ß1) in these samples was analyzed by RT-qPCR. The prognostic value of NBR2 for NSCLC was explored by performing a 5-year follow-up study. The interaction between NBR2 and TGF-ß1 in two NSCLC cell lines was detected by overexpression assay, followed by RT-qPCR and Western blot analysis. Flow cytometry was performed to evaluate the role of NBR2 and TGF-ß1 in regulating NSCLC cell stemness. RESULTS: NBR2 was significantly downregulated in NSCLC tissues than that in non-cancer tissues of NSCLC patients, and low expression levels of NBR2 predicted poor survival. TGF-ß1 was significantly upregulated in NSCLC tissues than that in non-cancer tissues, and was inversely correlated with NBR2. Overexpression of NBR2 downregulated TGF-ß1, while overexpression of TGF-ß1 did not affect the expression of NBR2. Overexpression of NBR2 inhibited, while overexpression of TGF-ß1 promoted NSCLC cell stemness. Overexpression of TGF-ß1 attenuated the effects of overexpression of NBR2. Mechanically, NBR2 interacted with Notch1 protein to inhibit its expression, thereby inhibiting the expression of TGF-ß1 and further affecting the proportion of CD133+ cells. CONCLUSION: LncRNA NBR2 regulates cancer cell stemness and predicts survival in NSCLC possibly by downregulating TGF-ß1 through Notch1.