RER1 enhances carcinogenesis and stemness of pancreatic cancer under hypoxic environment

RER1 在缺氧环境下增强胰腺癌的致癌作用和干性

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作者:Shi Chen, Jiaqiang Zhang, Jiangzhi Chen, Yaodong Wang, Songqiang Zhou, Long Huang, Yannan Bai, Chenghong Peng, Baiyong Shen, Huixing Chen, Yifeng Tian

Background

Increasing incidence and mortality rates of pancreatic cancer (PC) highlight an urgent need for novel and efficient drugs. Retention in endoplasmic reticulum 1 (RER1) is an important retention factor in the endoplasmic reticulum (ER). However, it remains elusive whether RER1 is involved in the retention of disease-related proteins.

Conclusion

The present study has demonstrated that RER1 enhances the progression of PC through promoting cell proliferation, migration and aggressiveness.

Methods

We analyzed the expression level of RER1 in PC and adjacent tissues, and also employed Kaplan-Meier's analysis to identify the correlation between RER1 expression and overall survival rate. Cell proliferation, colony formation, tumor formation, scratch test, and transwell invasion assays were performed in RER1 knockdown cells and negative control cells.

Results

We hereby reported the important functions of RER1 in tumorigenesis and metastasis of PC, evidenced by inhibitory effects of RER1 knockdown on PC cell proliferation, migration and aggressiveness. Tumor formation was also significantly repressed in RER1 knockdown cells compared to control. Hypoxia-inducible factor (HIF)-1α was found to be an upstream regulator of RER1. Knockdown HIF-1α cells exhibited similar repressive impact on cell proliferation as RER1, and showed diminished migratory and invasive abilities under hypoxic condition.

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