| Autor: |
Ling He, Xiangjun Zhou, Jia Liu, Yina Yao, Junyuan Lin, Jialong Chen, Shizhen Qiu, Zeyu Liu, Yingzheng He, Yujie Yi, Xueqiong Zhou, Fei Zou |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Ecotoxicology and Environmental Safety, Vol 265, Iss , Pp 115513- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
0147-6513 |
| DOI: |
10.1016/j.ecoenv.2023.115513 |
| Popis: |
Abstractc: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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