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Exosomal miR-19a decreases insulin production by targeting Neurod1 in pancreatic cancer associated diabetes

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Abstract

Background

New onset diabetes mellitus demonstrates a roughly correlation with pancreatic cancer (PaC), which is unique in PaC and was named as PaC-induced DM, but the inner mechanism remains unclear. Exosomes mediate intercellular communication and bearing microRNAs might be direct constituent of effect in target cells.

Methods and results

The isolated exosomes from PaC cells were used to treat pancreatic β cells or the primary mice islets, and the glucose stimulated insulin secretions were measured. We validated the exosomal miR-19a from PaC cells to be an important mediator in the down regulation of insulin secretion by targeting Neurod1, the validated gene involved in insulin secretion, by using the quantitative real-time PCR, western blot, and promoter luciferase activity. The relative insulin, cAMP and Ca2+ expressions were also assayed to verify the inverse correlation between cancerous miR-19a and pancreatic islets Neurod1.

Conclusions

Our study indicated that signal changes between cancer cells and β cells via exosomes might be important in the pathogenesis of PaC-induced DM and supplemented the pathogenesis of PaC-induced DM and provide a possible access of PaC screening strategy.

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Funding

This work was funded by the National Natural Science Foundation of China (81802304/H1617).

Author information

Author notes

  1. Jiaojiao Su and Wenjing Pang contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Lu’an Hospital of Anhui Medical University, Lu’an, China

    Jiaojiao Su

  2. Department of Gastroenterology, Lu’an People’s Hospital of Anhui Province, Lu’an, China

    Jiaojiao Su

  3. Digestive Disease Research and Clinical Translation Center, Shanghai Jiaotong University, Shanghai, China

    Wenjing Pang & Lei Li

  4. Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical, Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

    Aisen Zhang

  5. Department of Gerontology, Jiangsu People’s Hospital Affiliating to Nanjing Medical University, Nanjing, China

    Aisen Zhang

  6. Department of Gastroenterology, Shanghai Jiaotong University School of Medicine Affiliating Shanghai Ruijin Hospital, Shanghai, China

    Weiyan Yao & Xin Dai

  7. Department of Gastroenterology, Shanghai Jiaotong University School of Medicine Affiliating Shanghai 9th People’s Hospital, 639, Zhi Zao Ju Road, Shanghai, 200001, China

    Wenjing Pang & Lei Li

Authors
  1. Jiaojiao Su
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  2. Wenjing Pang
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  3. Aisen Zhang
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  4. Lei Li
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  5. Weiyan Yao
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  6. Xin Dai
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Corresponding authors

Correspondence to Wenjing Pang or Xin Dai.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Su, J., Pang, W., Zhang, A. et al. Exosomal miR-19a decreases insulin production by targeting Neurod1 in pancreatic cancer associated diabetes. Mol Biol Rep 49, 1711–1720 (2022). https://doi.org/10.1007/s11033-021-06980-z

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  • DOI: https://doi.org/10.1007/s11033-021-06980-z

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