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Research Paper|Volume 13, Issue 10|pp 14456—14468

Cancer-associated fibroblasts secreted miR-103a-3p suppresses apoptosis and promotes cisplatin resistance in non-small cell lung cancer

Haifeng Wang1, Haibo Huang1, Lijiang Wang2, Yan Liu2, Ming Wang3, Shasha Zhao3, Guangjian Lu4, Xiaohong Kang5
  • 1Third Ward of Oncology Department, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China
  • 2Respiratory Ward 2, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China
  • 3Respiratory Intensive Care Unit, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China
  • 4Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China
  • 5First Ward of Oncology Department, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China
Received: March 20, 2020Accepted: June 4, 2020Published: May 17, 2021
https://doi.org/10.18632/aging.103556

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: The cisplatin resistance of non-small cell lung cancer (NSCLC) patients results in low response rate and overall survival rate. Exosomes contribute to pathological processes of multiple cancers.

Objective: In this study, we explored the function and mechanisms of exosomal miR-103a-3p derived from cancer-associated fibroblast (CAF) in cisplatin resistance in NSCLC.

Results: MiR-103a-3p was highly expressed in CAFs and CAF exosomes, and exosomal miR-103a-3p derived from CAFs in NSCLC. CAFs exosomes co-cultured with NSCLC cells promoted miR-103a-3p expression both in NSCLC cells and its exosomes. Functional experiments showed that exo-miR-103a-3p derived from CAFs promoted cisplatin resistance and inhibited apoptosis in NSCLC cells. Pumilio2 (Pum2) bound with miR-103a-3p in cytoplasm and nucleus, and facilitated packaging into CAF-derived exosomes in NSCLC cells. Further analysis showed Bak1 was a direct target of miR-103a-3p, and miR-103a-3p accelerated cisplatin resistance in NSCLC cells via Bak1 downregulation. In vivo tumorigenesis assay showed CAF-derived exosomal miR-103a-3p enhanced cisplatin resistance and inhibited cell apoptosis in NSCLC.

Conclusion: Our study revealed that CAFs-derived exosomal miR-103a-3p promoted cisplatin resistance by suppressing apoptosis via targeting Bak1, which provided a potential therapeutic target for cisplatin resistance in NSCLC.