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miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39

Cancer Gene Therapy (2024)Cite this article

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Abstract

Exosomes are emerging mediators of cell-cell communication, which are secreted from cells and may be delivered into recipient cells in cell biological processes. Here, we examined microRNA (miRNA) expression in esophageal squamous cell carcinoma (ESCC) cells. We performed miRNA sequencing in exosomes and cells of KYSE150 and KYSE450 cell lines. Among these differentially expressed miRNAs, 20 of the miRNAs were detected in cells and exosomes. A heat map indicated that the level of miR-451a was higher in exosomes than in ESCC cells. Furthermore, miRNA pull-down assays and combined exosomes proteomic data showed that miR-451a interacts with YWHAE. Over-expression of YWHAE leads to miR-451a accumulation in the exosomes instead of the donor cells. We found that miR-451a was sorted into exosomes. However, the biological function of miR-451a remains unclear in ESCC. Here, Dual-luciferase reporter assay was conducted and it was proved that CAB39 is a target gene of miR-451a. Moreover, CAB39 is related to TGF-β1 from RNA-sequencing data of 155 paired of ESCC tissues and the matched tissues. Western Blot and qPCR revealed that CAB39 and TGF-β1 were positively correlated in ESCC. Over-expression of CAB39 were cocultured with PBMCs from the blood from healthy donors. Flow cytometry assays showed that apoptotic cells were significantly reduced after CAB39 over-expression and significantly increased after treated with TGF-β1 inhibitors. Thus, our data indicate that CAB39 weakens antitumor immunity through TGF-β1 in ESCC. In summary, YWHAE selectively sorted miR-451a into exosomes and it can weaken antitumor immunity promotes tumor progression through CAB39.

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Fig. 1: miR-451a was selectively sorted into exosomes.
Fig. 2: Sorting of miR-451a from cells to exosomes through YWHAE.
Fig. 3: CAB39 is a direct target of miR-451a in esophageal squamous cell carcinoma.
Fig. 4: CAB39 is inversely correlated with TGF-β1 expression in ESCC.
Fig. 5: CAB39 weakens the sensitivity of PBMCs through TGF-β1 in the co-culture model.
Fig. 6: CAB39 promoted tumor growth expression and was correlated with TGF-β1 in mice.
Fig. 7: The mechanism of miR-451a sorted into exosomes by YWHAE in ESCC.

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Data availability

All raw data that support the findings of this study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the Shanxi Medical University Key Laboratory of the Ministry of Education for providing us with the Cell physiology equipment platform.

Funding

This work was supported by the Fundamental Research Program of Shanxi Province (20210302123292); the Central Guidance on Local Science and Technology Development Fund of Shanxi Province (YDZJSX2021A018); and the innovative project of graduate education in Shanxi province (2022Y366).

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Authors and Affiliations

  1. Translational Medicine Research Center, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Lu Wang, Huijuan Liu, Qinglu Wu, Yiqian Liu, Zhenpeng Yan, Guohui Chen, Yao Shang, Songrui Xu, Qichao Zhou, Ting Yan & Xiaolong Cheng

  2. Key Laboratory of Cellular Physiology of the Ministry of Education, Department of Pathology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Lu Wang, Huijuan Liu, Qinglu Wu, Yiqian Liu, Zhenpeng Yan, Guohui Chen, Yao Shang, Songrui Xu, Qichao Zhou, Ting Yan & Xiaolong Cheng

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Contributions

Xiaolong Cheng and Ting Yan: formal analysis, funding acquisition, project administration; Lu Wang: data curation, validation, writing-original draft. Huijuan Liu, Qinglu Wu, and Yiqian Liu: supervision, visualization, revised and edited the manuscript. Zhenpeng Yan, Guohui Chen, and Yao Shang: formal analysis, investigation. Songrui Xu and Qichao Zhou: supervision, conceptualization.

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Correspondence to Ting Yan or Xiaolong Cheng.

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Wang, L., Liu, H., Wu, Q. et al. miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00774-8

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