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Human umbilical cord mesenchymal stem cell-derived extracellular vesicles carrying miR-655-3p inhibit the development of esophageal cancer by regulating the expression of HIF-1α via a LMO4/HDAC2-dependent mechanism

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Abstract

Objective

This study clarified the function of human umbilical cord mesenchymal stem cell (hUCMSC)-derived extracellular vesicle (EV)-enclosed miR-655-3p in esophageal squamous cell carcinoma (ESCC).

Methods

A Chi-square test and the Kaplan–Meier estimator were used to analyze the prognosis of ESCC in relation to the expression of miR-655-3p. ESCC cells were incubated with PBS or hUCMSC-derived EVs (hUCMSC-EVs) in the conditions of gene modification, after which the malignant behaviors of ESCC cells were assessed and the molecular interactions were determined. The effect of hUCMSC-derived EV-miR-655-3p was also investigated in a nude mouse model of ESCC.

Results

Low expression of miR-655-3p indicated poor prognosis of ESCC. hUCMSC-EVs suppressed the malignant behaviors of ESCC cells and the growth and liver metastasis of transplanted tumors. Inhibition of miR-655-3p in hUCMSCs impaired the therapeutic effect of hUCMSC-EVs. LMO4, targeted by miR-655-3p, activated the transcription of HIF-1α by sequestering HDAC2 from HIF-1α promoter. Knockdown of LMO4 suppressed ESCC cell activities, while overexpression of HIF-1α counteracted the tumor suppressive effect of LMO4 knockdown.

Conclusion

miR-655-3p enclosed in hUCMSC-derived EVs inhibits ESCC progression partially by inactivating HIF-1α via the LMO4/HDAC2 axis.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

References

  • Albadari N, Deng S, Li W. The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy. Expert Opin Drug Discov. 2019;14(7):667–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bush EW, McKinsey TA. Protein acetylation in the cardiorenal axis: the promise of histone deacetylase inhibitors. Circ Res. 2010;106(2):272–84.

    Article  CAS  PubMed  Google Scholar 

  • Cai X, Zhao Z, Dong J, Lv Q, Yun B, Liu J, Shen Y, et al. Circular RNA circBACH2 plays a role in papillary thyroid carcinoma by sponging miR-139-5p and regulating LMO4 expression. Cell Death Dis. 2019;10(3):184.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chang P, Wang X, Zhou Y, Hou Y. Analysis of the correlation between the expression of miR-655 and esophageal cancer prognosis. Oncol Lett. 2017;13(6):4691–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen T, Li K, Liu Z, Liu J, Wang Y, Sun R, Li Z, et al. WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1alpha accumulation in Myc-dependent and independent pathways. Mol Ther. 2021;29(6):2134–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen W, Huang L, Liang J, Ye Y, Yu S, Zhang Y. Long noncoding RNA small nucleolar RNA host gene 15 deteriorates liver cancer via microRNA-18b-5p/LIM-only 4 axis. IUBMB Life. 2021b;73(2):349–61.

    Article  CAS  PubMed  Google Scholar 

  • Ding DC, Chang YH, Shyu WC, Lin SZ. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transplant. 2015;24(3):339–47.

    Article  PubMed  Google Scholar 

  • Gao S, Zhao ZY, Zhang ZY, Zhang Y, Wu R. Prognostic Value of MicroRNAs in Esophageal Carcinoma: A Meta-Analysis. Clin Transl Gastroenterol. 2018;9(11):203.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao G, Wang L, Li C. Circ_0006790 carried by bone marrow mesenchymal stem cell-derived exosomes regulates S100A11 DNA methylation through binding to CBX7 in pancreatic ductal adenocarcinoma. Am J Cancer Res. 2022;12(5):1934–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Manrique P, Gutierrez G, Blanco-Lopez MC. Fully Artificial Exosomes: Towards New Theranostic Biomaterials. Trends Biotechnol. 2018;36(1):10–4.

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Smith M, Qin Z, Zhou X, Schock SC, Chen HH. LIM domain only 4 protein promotes granulocyte colony-stimulating factor-induced signaling in neurons. Cell Mol Life Sci. 2010;67(6):949–57.

    Article  CAS  PubMed  Google Scholar 

  • Han L, Cui D, Li B, Xu WW, Lam AKY, Chan KT, Zhu Y, et al. MicroRNA-338-5p reverses chemoresistance and inhibits invasion of esophageal squamous cell carcinoma cells by targeting Id-1. Cancer Sci. 2019;110(12):3677–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harazono Y, Muramatsu T, Endo H, Uzawa N, Kawano T, Harada K, Inazawa J, et al. miR-655 Is an EMT-suppressive microRNA targeting ZEB1 and TGFBR2. PLoS ONE. 2013;8(5):e62757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He C, Zheng S, Luo Y, Wang B. Exosome Theranostics: Biology and Translational Medicine. Theranostics. 2018;8(1):237–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Z, Li W, Zheng T, Liu D, Zhao S. Human umbilical cord mesenchymal stem cells-derived exosomes deliver microRNA-375 to downregulate ENAH and thus retard esophageal squamous cell carcinoma progression. J Exp Clin Cancer Res. 2020;39(1):140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu X, Lin J, Jiang M, He X, Wang K, Wang W, Hu C, et al. HIF-1alpha Promotes the Metastasis of Esophageal Squamous Cell Carcinoma by Targeting SP1. J Cancer. 2020;11(1):229–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang FL, Yu SJ. Esophageal cancer: Risk factors, genetic association, and treatment. Asian J Surg. 2018;41(3):210–5.

    Article  PubMed  Google Scholar 

  • Jia Y, Ding X, Zhou L, Zhang L, Yang X. Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1. Oncogene. 2021;40(2):246–61.

    Article  CAS  PubMed  Google Scholar 

  • Jiang S, Mo C, Guo S, Zhuang J, Huang B, Mao X. Human bone marrow mesenchymal stem cells-derived microRNA-205-containing exosomes impede the progression of prostate cancer through suppression of RHPN2. J Exp Clin Cancer Res. 2019;38(1):495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kiuchi J, Komatsu S, Imamura T, Nishibeppu K, Shoda K, Arita T, Kosuga T, et al. Low levels of tumour suppressor miR-655 in plasma contribute to lymphatic progression and poor outcomes in oesophageal squamous cell carcinoma. Mol Cancer. 2019;18(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lam AK. Introduction: Esophageal Squamous Cell Carcinoma-Current Status and Future Advances. Methods Mol Biol. 2020;2129:1–6.

    Article  CAS  PubMed  Google Scholar 

  • Lee JK, Park SR, Jung BK, Jeon YK, Lee YS, Kim MK, Kim YG, et al. Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS ONE. 2013;8(12):e84256.

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu L, Yan C, Tao S, Wang H. Circ_0058124 Aggravates the Progression of Papillary Thyroid Carcinoma by Activating LMO4 Expression via Targeting miR-370-3p. Cancer Manag Res. 2020;12:9459–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu YR, Song J, Zhabihula BX, Zhang JR. 2-Methoxyestradiol promotes radiosensitivity of esophageal squamous cell carcinoma by suppressing hypoxia-inducible factor-1alpha expression. Eur Rev Med Pharmacol Sci. 2019;23(24):10785–95.

    PubMed  Google Scholar 

  • Luo ., von der Ohe J, & Hass R. MSC-Derived Extracellular Vesicles in Tumors and Therapy. Cancers (Basel). 2021;13(20).

  • Lv ZD, Kong B, Liu XP, Jin LY, Dong Q, Li FN, Wang HB. miR-655 suppresses epithelial-to-mesenchymal transition by targeting Prrx1 in triple-negative breast cancer. J Cell Mol Med. 2016;20(5):864–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lv Z, Liu RD, Chen XQ, Wang B, Li LF, Guo YS, Chen XJ, et al. HIF1alpha promotes the stemness of oesophageal squamous cell carcinoma by activating the Wnt/betacatenin pathway. Oncol Rep. 2019;42(2):726–34.

    CAS  PubMed  Google Scholar 

  • Maguire G. Stem cell therapy without the cells. Commun Integr Biol. 2013;6(6):e26631.

    Article  PubMed  PubMed Central  Google Scholar 

  • Malhotra GK, Yanala U, Ravipati A, Follet M, Vijayakumar M, Are C. Global trends in esophageal cancer. J Surg Oncol. 2017;115(5):564–79.

    Article  PubMed  Google Scholar 

  • Pakravan K, Babashah S, Sadeghizadeh M, Mowla SJ, Mossahebi-Mohammadi M, Ataei F, Dana N, et al. MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1alpha/VEGF signaling axis in breast cancer cells. Cell Oncol (dordr). 2017;40(5):457–70.

    Article  CAS  PubMed  Google Scholar 

  • Peng C, Cohen DJ. Advances in the pharmacotherapeutic management of esophageal squamous cell carcinoma. Expert Opin Pharmacother. 2021;22(1):93–107.

    Article  CAS  PubMed  Google Scholar 

  • Phinney DG, Pittenger MF. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells. 2017;35(4):851–8.

    Article  CAS  PubMed  Google Scholar 

  • Qin F, Tang H, Zhang Y, Zhang Z, Huang P, Zhu J. Bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-208a promotes osteosarcoma cell proliferation, migration, and invasion. J Cell Physiol. 2020;235(5):4734–45.

    Article  CAS  PubMed  Google Scholar 

  • Reichenbach ZW, Murray MG, Saxena R, Farkas D, Karassik EG, Klochkova A, Patel K, et al. Clinical and translational advances in esophageal squamous cell carcinoma. Adv Cancer Res. 2019;144:95–135.

    Article  CAS  PubMed  Google Scholar 

  • Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16(3):203–22.

    Article  CAS  PubMed  Google Scholar 

  • Sang M, Ma L, Sang M, Zhou X, Gao W, Geng C. LIM-domain-only proteins: multifunctional nuclear transcription coregulators that interacts with diverse proteins. Mol Biol Rep. 2014;41(2):1067–73.

    Article  CAS  PubMed  Google Scholar 

  • Shen Y, Wei W, Zhou DX. Histone Acetylation Enzymes Coordinate Metabolism and Gene Expression. Trends Plant Sci. 2015;20(10):614–21.

    Article  CAS  PubMed  Google Scholar 

  • Short MW, Burgers KG, Fry VT. Esophageal Cancer. Am Fam Physician. 2017;95(1):22–8.

    PubMed  Google Scholar 

  • Simonik EA, Cai Y, Kimmelshue KN, Brantley-Sieders DM, Loomans HA, Andl CD, Westlake GM, et al. LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer). PLoS ONE. 2016;11(10):e0164804.

    Article  PubMed  PubMed Central  Google Scholar 

  • Staufer O, Hernandez Bucher JE, Fichtler J, Schroter M, Platzman I, Spatz JP. Vesicle Induced Receptor Sequestration: Mechanisms behind Extracellular Vesicle-Based Protein Signaling. Adv Sci (weinh). 2022;9(13):e2200201.

    Article  PubMed  Google Scholar 

  • Staufer O, Dietrich F, Rimal R, Schroter M, Fabritz S, Boehm H, Singh S et al. Bottom-up assembly of biomedical relevant fully synthetic extracellular vesicles. Sci Adv. 2021;7(36):eabg6666.

  • Sun G, Hu W, Lu Y, Wang Y. A meta-analysis of HIF-1alpha and esophageal squamous cell carcinoma (ESCC) risk. Pathol Oncol Res. 2013;19(4):685–93.

    Article  CAS  PubMed  Google Scholar 

  • Thery C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vaupel P, Multhoff G. Fatal Alliance of Hypoxia-/HIF-1alpha-Driven Microenvironmental Traits Promoting Cancer Progression. Adv Exp Med Biol. 2020;1232:169–76.

    Article  CAS  PubMed  Google Scholar 

  • Visvader JE, Venter D, Hahm K, Santamaria M, Sum EY, O’Reilly L, White D, et al. The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer. Proc Natl Acad Sci U S A. 2001;98(25):14452–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang N, Lin KK, Lu Z, Lam KS, Newton R, Xu X, Yu Z, et al. The LIM-only factor LMO4 regulates expression of the BMP7 gene through an HDAC2-dependent mechanism, and controls cell proliferation and apoptosis of mammary epithelial cells. Oncogene. 2007;26(44):6431–41.

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Wu S, Guo M, He J. LMO4 is a prognostic marker involved in cell migration and invasion in non-small-cell lung cancer. J Thorac Dis. 2016;8(12):3682–90.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang N, Dong Q, Zhou XN. LMO4 promotes the invasion and proliferation of gastric cancer by activating PI3K-Akt-mTOR signaling. Am J Transl Res. 2019;11(10):6534–43.

    PubMed  PubMed Central  Google Scholar 

  • Wang W, Cao R, Su W, Li Y, Yan H. miR-655-3p inhibits cell migration and invasion by targeting pituitary tumor-transforming 1 in non-small cell lung cancer. Biosci Biotechnol Biochem. 2019;83(9):1703–8.

    Article  CAS  PubMed  Google Scholar 

  • Wang WW, Zhao ZH, Wang L, Li P, Chen KS, Zhang JY, Li WC, et al. Corrigendum to “MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway” [EBioMedicine 46 (2019) 66–78]. EBioMedicine. 2020;55: 102772.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Xie Z, Lu H. Significance of halofuginone in esophageal squamous carcinoma cell apoptosis through HIF-1alpha-FOXO3a pathway. Life Sci. 2020;257: 118104.

    Article  CAS  PubMed  Google Scholar 

  • Weng Z, Zhang B, Wu C, Yu F, Han B, Li B, Li L. Therapeutic roles of mesenchymal stem cell-derived extracellular vesicles in cancer. J Hematol Oncol. 2021;14(1):136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu G, Zheng K, Xia S, Wang Y, Meng X, Qin X, Cheng Y. MicroRNA-655-3p functions as a tumor suppressor by regulating ADAM10 and beta-catenin pathway in Hepatocellular Carcinoma. J Exp Clin Cancer Res. 2016;35(1):89.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu DM, Wen X, Han XR, Wang S, Wang YJ, Shen M, Fan SH, et al. Bone Marrow Mesenchymal Stem Cell-Derived Exosomal MicroRNA-126-3p Inhibits Pancreatic Cancer Development by Targeting ADAM9. Mol Ther Nucleic Acids. 2019;16:229–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu H, Zhao G, Zhang Y, Jiang H, Wang W, Zhao D, Hong J, et al. Mesenchymal stem cell-derived exosomal microRNA-133b suppresses glioma progression via Wnt/beta-catenin signaling pathway by targeting EZH2. Stem Cell Res Ther. 2019;10(1):381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Y, Lai Y, Cao L, Li Y, Chen G, Chen L, Weng H et al. Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-451a represses epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting ADAM10. RNA Biol. 2020;1–16.

  • Yaghoubi Y, Movassaghpour A, Zamani M, Talebi M, Mehdizadeh A, Yousefi M. Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment. Life Sci. 2019;233:116733.

    Article  CAS  PubMed  Google Scholar 

  • Zha JF, Chen DX. MiR-655-3p inhibited proliferation and migration of ovarian cancer cells by targeting RAB1A. Eur Rev Med Pharmacol Sci. 2019;23(9):3627–34.

    PubMed  Google Scholar 

  • Zhang D, Wei Y, Zhou J, Wang G, Xiao L, Xu J, Wei N, et al. miR-150 might inhibit cell proliferation and promote cell apoptosis by targeting LMO4 in Burkitt lymphoma. J Cell Physiol. 2019;234(6):9652–62.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P. Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications. Int J Nanomedicine. 2020;15:6917–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang F, Guo J, Zhang Z, Qian Y, Wang G, Duan M, Zhao H, et al. Mesenchymal stem cell-derived exosome: A tumor regulator and carrier for targeted tumor therapy. Cancer Lett. 2022;526:29–40.

    Article  CAS  PubMed  Google Scholar 

  • Zhao Z, Yang S, Cheng Y, Zhao X. MicroRNA655 inhibits cell proliferation and invasion in epithelial ovarian cancer by directly targeting vascular endothelial growth factor. Mol Med Rep. 2018;18(2):1878–84.

    CAS  PubMed  Google Scholar 

  • Zhao X, Tang YP, Wang CY, Wu JX, Ye F. Prognostic values of STAT3 and HIF-1alpha in esophageal squamous cell carcinoma. Eur Rev Med Pharmacol Sci. 2019;23(8):3351–7.

    CAS  PubMed  Google Scholar 

  • Zhu W, Huang L, Li Y, Zhang X, Gu J, Yan Y, Xu X, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 2012;315(1):28–37.

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Zang Y, Zhao F, Li Z, Zhang J, Fang L, Li M, et al. Inhibition of HIF-1alpha by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo. Am J Cancer Res. 2017;7(5):1198–212.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu T, Hu Z, Wang Z, Ding H, Li R, Wang J, & Wang G. microRNA-301b-3p from mesenchymal stem cells-derived extracellular vesicles inhibits TXNIP to promote multidrug resistance of gastric cancer cells. Cell Biol Toxicol. 2022.

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Acknowledgements

The authors thank Professor Yuan Yunchang for his valuable comments on the article and thank the Thoracic Surgery Laboratory for providing the experimental site and reagents free of charge.

Funding

The authors thank for the grant from the Innovative research and development project of Department and Reform Commission of Hunan Province.

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Authors and Affiliations

  1. Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China

    Mingjiu Chen & Zhenkun Xia

  2. Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, Hunan, 410005, People’s Republic of China

    Jie Deng

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  1. Mingjiu Chen
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Contributions

CMJ conceived the ideas. DJ designed the experiments. CMJ performed the experiments. DJ analyzed the data. CMJ and XZK provided critical materials. DJ and XZK wrote the manuscript. CMJ supervised the study. All the authors have read and approved the final version for publication.

Corresponding author

Correspondence to Jie Deng.

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The collection and use of human tissues were authorized by the ethics committee of The First Hospital of Changsha in consistent with the Declaration of Helsinki. All patients signed informed consents for the sample collection. All animal experiments were conducted under the rules and ethical requirements of laboratory animal management, with approval from the ethics committee of The First Hospital of Changsha.

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Highlights 

• Low expression of miR-655-3p in ESCC patients indicates poor prognosis.

• hUCMSC-derived EV-carrying miR-655-3p suppresses ESCC in vivo and in vitro.

• miR-655-3p negatively regulates the expression of LMO4 in a targeted manner.

• LMO4 activates HIF-1α transcription by sequestering HDAC2 from HIF-1α promoter

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Chen, M., Xia, Z. & Deng, J. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles carrying miR-655-3p inhibit the development of esophageal cancer by regulating the expression of HIF-1α via a LMO4/HDAC2-dependent mechanism. Cell Biol Toxicol 39, 1319–1339 (2023). https://doi.org/10.1007/s10565-022-09759-5

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  • DOI: https://doi.org/10.1007/s10565-022-09759-5

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