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AGR2-induced glucose metabolism facilitated the progression of endometrial carcinoma via enhancing the MUC1/HIF-1α pathway

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Abstract

Anterior gradient 2 (AGR2) was proved to modulate cancer progression. However, the role of AGR2 on endometrial cancer was not established. Here, we investigated the effects of AGR2 expression on endometrial cancer and explored the regulation mechanism. In the study, we found that AGR2 was overexpressed in tumor tissues of 30 endometrial cancer patients. A high level of AGR2 promoted endometrial cancer cells proliferation, migration and invasion. AGR2 induced the expression of lactate dehydrogenase A (LDHA), phosphoglycerate kinase 1 (PGK1), kallikrein 2 (HK2), and enolase 1-α (ENO1), glucose uptake and lactate production. AGR2 could bind to MUC1 and induce MUC1 and hypoxia-inducible factor 1α (HIF-1α). The inhibition effects of AGR2 knockdown on cells proliferation, migration and invasion ability were abolished by the overexpression of MUC1. Besides, the overexpression of MUC1 also reversed the inhibition effects of AGR2 knockdown on the expression of LDHA, HK2, PGK1 and ENO1, glucose uptake and lactate production. AGR2 knockdown inhibited tumor growth, the levels of Ki-67, MUC1, HIF-1α and glycolysis. In conclusion, AGR2 was overexpressed in endometrial cancer and AGR2-induced glucose metabolism facilitated the progression of endometrial carcinoma via the MUC1/HIF-1α pathway. AGR2 may be an effective therapeutic target for endometrial carcinoma.

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Authors and Affiliations

  1. Department of Gynaecology, The Fourth Affiliated Hospital of Xinjiang Medical University, No. 116 Huanghe Road, Tianshan District, Urumqi City, 830000, Xinjiang Uygur Autonomous Region, China

    Wei Gong, Belize Ekmu, Xinmei Wang, Yanli Lu & Li Wan

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  1. Wei Gong
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  2. Belize Ekmu
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  3. Xinmei Wang
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  4. Yanli Lu
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  5. Li Wan
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Contributions

WG conceived and designed the experiments, BE and XW analyzed and interpreted the results of the experiments, and YL and LW performed the experiments.

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Correspondence to Wei Gong.

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The authors declare that they have no competing interests, and all authors would confirm its accuracy.

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The protocol of the study was approved by the Ethics Committee of The Fourth Affiliated Hospital of Xinjiang Medical University (No. 2017065), and all the patients signed written informed consent.

All animal experiments were approved by the Ethics Committee of The Fourth Affiliated Hospital of Xinjiang Medical University (No. 2017065).

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Gong, W., Ekmu, B., Wang, X. et al. AGR2-induced glucose metabolism facilitated the progression of endometrial carcinoma via enhancing the MUC1/HIF-1α pathway. Human Cell 33, 790–800 (2020). https://doi.org/10.1007/s13577-020-00356-4

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