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Exosome-derived miR-200a promotes esophageal cancer cell proliferation and migration via the mediating Keap1 expression

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Abstract

Previous studies have reported that exosomes bearing certain microRNAs (miRNAs) are related to the physiological functions of different types of cancer cells. Our study aimed to elucidate the role of miR-200a in esophageal squamous cell carcinoma (ESCC). We observed that miR-200a expression is higher in esophageal carcinoma cells, tissues, and exosomes than in normal cells and healthy tissues. We showed that exosome-shuttled miR-200a promotes the proliferation, migration, and invasion of esophageal cells and inhibits apoptosis, thereby leading to the progression of ESCC. We showed that miR-200a exerts its effects through its interaction with Keap1, thus altering the Keap1/Nrf2 signaling pathway. Our results suggest that exosome-shuttled miR-200a might be useful as a biomarker for prognosis in patients with ESCC.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, 127 Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China

    Peng Li, Xianben Liu, Wenqun Xing, Shilei Liu & Haibo Sun

  2. Quality and Standards Academy, Shenzhen Technology University, Shenzhen, 518000, Guangdong, China

    Huiling Qiu & Renling Li

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  1. Peng Li
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Contributions

PL, XL, and WX conceived and designed the research. PL, XL, WX, HQ, RL, SL, and HS performed experiments, interpreted the results of experiments, and analyzed data. PL edited and revised the manuscript.

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Correspondence to Peng Li.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital and written informed consent was obtained from all patients. All animal experiments were performed in accordance with the International Commission Guidelines for the Care and Use of Laboratory Animals.

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Informed consent was obtained from all individual participants included in the study.

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Supplementary Information

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11010_2022_4353_MOESM1_ESM.tif

Supplementary file1 (TIF 7422 kb) Exosome isolated from EC9706 cells and HEECs. TEM images of exosomes derived from EC9706 cells and HEECs

11010_2022_4353_MOESM2_ESM.tif

Supplementary file2 (TIF 113 kb) MiR-200a level in purified exosome from EC9706 cells and HEECs. qPCR was carried out to examine the miR-200a level in purified exosome from EC9706 cells and HEECs

11010_2022_4353_MOESM3_ESM.tif

Supplementary file3 (TIF 185 kb) Effect of co-culture system on the miR-200a level in donor EC9706 cells, purified exosomes, and recipient EC9706 cells. Donor EC9706 cells were transfected with miR-200a mimic/inhibitor (100 nM) or NC mimic/inhibitor (100 nM) for 24 h and then subjected to co-culture system. The exosomes derived from donor cells were also purified. (A, B, C) qPCR quantification of miR-200a levels in donor ESCC EC9706 cells, exosomes, and recipient EC9706 cells. * p < 0.05, ** p < 0.01, *** p < 0.001. Data are shown as mean ± standard deviation, and one-way ANOVA and Tukey’s post hoc test were used to compare multiple groups. Experiments were performed three times

11010_2022_4353_MOESM4_ESM.tif

Supplementary file4 (TIF 11726 kb) Co-culture system affected the proliferation, apoptosis, migration, and invasion of EC9706 cells and reduced apoptosis. (A) EdU staining assay to assess the proliferation of recipient ESCC EC9706 cells. (B) CFA to examine the colony formation ability of recipient cells. (C) FC assay to detect apoptosis of recipient EC9706 cells in each group. (D) Wound healing assay to assess the migration of recipient EC9706 cells in two groups. (E) Transwell assay to examine the invasion of recipient EC9706 cells in two groups. Donor EC9706 cells transfected with a miR-200a overexpression or inhibitor construct were co-cultured with recipient EC9706 cells. * p < 0.05, ** p < 0.01. Data are shown as mean ± standard deviation, and one-way ANOVA and Tukey’s post hoc test were used to compare multiple groups. Experiments were performed three times

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Li, P., Liu, X., Xing, W. et al. Exosome-derived miR-200a promotes esophageal cancer cell proliferation and migration via the mediating Keap1 expression. Mol Cell Biochem 477, 1295–1308 (2022). https://doi.org/10.1007/s11010-022-04353-z

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