LncRNA NBR2 Regulates Cancer Cell Stemness and Predicts Survival in Non-small Cell Cancer Patients by Downregulating TGF-β1

Author:

Wang Qiang1,Huang Jun1,Yu Qiuhua1,Zhang Junjie1,lu Wenbin2,Liu Qian2,Chu Ying3,Zhou Yanjuan4,Tu Renshu5,Zhou Huxiang1

Affiliation:

1. Department of Cardio-Thoracic Surgery, Wujin Hospital Affiliated with Jiangsu University (The Wujin Clinical College of Xuzhou Medical University), Changzhou City, Jiangsu Provence,213017, China

2. Department of Oncology, Wujin Hospital Affiliated with Jiangsu University (The Wujin Clinical College of Xuzhou Medical University), Changzhou City, Jiangsu Provence, 213017, China

3. Department of Center Laboratory, Wujin Hospital Affiliated with Jiangsu University (The Wujin Clinical College of Xuzhou Medical University), Changzhou City, Jiangsu Provence, 213017, China

4. Department of Respiratory, Wujin Hospital Affiliated with Jiangsu University (The Wujin Clinical College of Xuzhou Medical University), Changzhou City, Jiangsu Provence, 213017, China

5. Department of Anesthesiology, Wujin Hospital Affiliated with Jiangsu University (The Wujin Clinical College of Xuzhou Medical University), Changzhou City, Jiangsu Provence, 213017, China

Abstract

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-β1 (TGF-β1) 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-β1 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-β1 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-β1 was significantly upregulated in NSCLC tissues than that in non-cancer tissues, and was inversely correlated with NBR2. Overexpression of NBR2 downregulated TGF-β1, while overexpression of TGF-β1 did not affect the expression of NBR2. Overexpression of NBR2 inhibited, while overexpression of TGF-β1 promoted NSCLC cell stemness. Overexpression of TGF-β1 attenuated the effects of overexpression of NBR2. Mechanically, NBR2 interacted with Notch1 protein to inhibit its expression, thereby inhibiting the expression of TGF-β1 and further affecting the proportion of CD133+ cells. Conclusion: LncRNA NBR2 regulates cancer cell stemness and predicts survival in NSCLC possibly by downregulating TGF-β1 through Notch1.

Publisher

Bentham Science Publishers Ltd.

Subject

Pharmaceutical Science,Biotechnology

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