Details

Autor(en) / Beteiligte

• He, Ling
• Zhou, Xiangjun
• Liu, Jia
• Yao, Yina
• Lin, Junyuan
• Chen, Jialong
• Qiu, Shizhen
• Liu, Zeyu
• He, Yingzheng
• Yi, Yujie
• Zhou, Xueqiong
• Zou, Fei

Titel

RAE1 promotes nitrosamine-induced malignant transformation of human esophageal epithelial cells through PPARα-mediated lipid metabolism

Ist Teil von

• Ecotoxicology and environmental safety, 2023-10, Vol.265, p.115513-115513, Article 115513

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2023

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Esophageal cancer (EC) is the sixth cause of cancer-related deaths and still is a significant public health problem globally. Nitrosamines exposure represents a major health concern increasing EC risks. Exploring the mechanisms induced by nitrosamines may contribute to the prevention and early detection of EC. However, the mechanism of nitrosamine carcinogenesis remains unclear. Ribonucleic acid export 1 (RAE1), has an important role in mediating diverse cancer types, but, to date, there has been no study for any functional role of RAE1 in esophageal carcinogenesis. Here, we successfully verified the nitrosamine-induced malignant transformation cell (MNNG-M) by xenograft tumor model, based on which it was found that RAE1 was upregulation in the early stage of nitrosamine-induced esophageal carcinogenesis and EC tissues. RAE1 knockdown led to severe blockade in G2/M phase and significant inhibition of proliferation of MNNG-M cells, whereas RAE1 overexpression had the opposite effect. In addition, peroxisome proliferator-activated receptor-alpha (PPARα), was demonstrated as a downstream target gene of RAE1, and its down-regulation reduced lipid accumulation, resulting in causing cells accumulation in the G2/M phase. Mechanistically, we found that RAE1 regulates the lipid metabolism by maintaining the stability of PPARα mRNA. Taken together, our study reveals that RAE1 promotes malignant transformation of human esophageal epithelial cells (Het-1A) by regulating PPARα-mediated lipid metabolism to affect cell cycle progression, and offers a new explanation of the mechanisms underlying esophageal carcinogenesis. [Display omitted] •RAE1 expression was significantly increased in nitrosamine-induced esophageal carcinoma at the early stage.•RAE1 promotes abnormal proliferation during transformation of human esophageal epithelial cells induced by nitrosamine.•RAE1 regulates cell cycle progress to promote transformation properties.•PPARα is a downstream target of RAE1, and its mRNA stability depends on RAE1.•RAE1 mediating lipid metabolism through regulation of PPARα mRNA stability to involves in cell cycle process.