Exosomes Secreted from Mesenchymal Stem Cells Carry miR-486-5p to Inhibit Cell Proliferation and the Epithelial-Mesenchymal Transition Process to Treat Human Lung Cancer by Down-Regulating MIER3

Exosomes are nano-vesicles that can shuttle active cargoes. Mesenchymal stem cells play a complex function in tumour progression.We investigated the effect of miR-486-5p, an exosome of human bone marrow-derived MSCs on lung cancer. We found that miR-486-5p, carried in mesenchymal stem cells and mesenchymal stem cell-derived exosomes, regulates MIER3 expression by binding to its 3’UTR, thereby inhibiting the epithelial-mesenchymal transition process of A549 cells. In vivo, we demonstrated that exosome treatment reduced the area of tumour necrosis, increased the expression of miR-486-5p and inhibited the epithelial–mesenchymal transition process in mice. In conclusion, mesenchymal stem cell-derived exosomal miR-486-5p directly and negatively targets MIER3 to inhibit lung cancer.

[1]  H. Mithoowani,et al.  Non-Small-Cell Lung Cancer in 2022: A Review for General Practitioners in Oncology , 2022, Current oncology.

[2]  A. Jemal,et al.  Cancer Statistics, 2021 , 2021, CA: a cancer journal for clinicians.

[3]  Qiang Yu,et al.  Mesenchymal Stem Cell-Secreted Exosome Promotes Chemoresistance in Breast Cancer via Enhancing miR-21-5p-Mediated S100A6 Expression , 2020, Molecular therapy oncolytics.

[4]  Jian Kang,et al.  Let‐7b‐5p is involved in the response of endoplasmic reticulum stress in acute pulmonary embolism through upregulating the expression of stress‐associated endoplasmic reticulum protein 1 , 2020, IUBMB life.

[5]  T. Jiang,et al.  SNHG16 as the miRNA let‐7b‐5p sponge facilitates the G2/M and epithelial‐mesenchymal transition by regulating CDC25B and HMGA2 expression in hepatocellular carcinoma , 2019, Journal of cellular biochemistry.

[6]  L. Crinò,et al.  Epithelial‐to‐mesenchymal transition in the context of epidermal growth factor receptor inhibition in non‐small‐cell lung cancer , 2018, Biological reviews of the Cambridge Philosophical Society.

[7]  J. Hsieh,et al.  Exosomes in cancer development and clinical applications , 2018, Cancer science.

[8]  Roy S. Herbst,et al.  The biology and management of non-small cell lung cancer , 2018, Nature.

[9]  Xuetao Cao,et al.  Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils. , 2016, Cancer cell.

[10]  Yanning Liu,et al.  Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma , 2015, Journal of Hematology & Oncology.

[11]  S. Yeh,et al.  BM-MSCs promote prostate cancer progression via the conversion of normal fibroblasts to cancer-associated fibroblasts , 2015, International journal of oncology.

[12]  L. Pfeffer,et al.  MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity , 2015, Oncogene.

[13]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[14]  Sha Li,et al.  Exosome and Exosomal MicroRNA: Trafficking, Sorting, and Function , 2015, Genom. Proteom. Bioinform..

[15]  Kwok-Kin Wong,et al.  Non-small-cell lung cancers: a heterogeneous set of diseases , 2014, Nature Reviews Cancer.

[16]  Murray J. Cairns,et al.  Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons , 2014, Nucleic acids research.

[17]  Samy Lamouille,et al.  Molecular mechanisms of epithelial–mesenchymal transition , 2014, Nature Reviews Molecular Cell Biology.

[18]  Michael Chopp,et al.  Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. , 2013, Cancer letters.

[19]  T. Mikkelsen,et al.  Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal , 2013, Oncotarget.

[20]  J. Thiery Epithelial–mesenchymal transitions in tumour progression , 2002, Nature Reviews Cancer.

[21]  P. Grandjean,et al.  Organochlorine exposures influence on breast cancer risk and survival according to estrogen receptor status: a Danish cohort-nested case-control study , 2001, BMC Cancer.