microRNA-204 shuttled by mesenchymal stem cell-derived exosomes inhibits the migration and invasion of non-small-cell lung cancer cells via the KLF7/AKT/HIF-1α axis

Abstract

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide.Accumulating researches have highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the significance of mesenchymal stem cells (MSCs)-derived exosomal miR-204 in the invasion, migration, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Initially, the expression of miR-204 in human NSCLC tissues and cells was determined by RT-qPCR, which demonstrated that miR-204 was downregulated in NSCLC tissues and cells. Next, Krüppel-like factor 7 (KLF7) was predicted and validated to be a target of miR-204 using dual-luciferase reporter gene assay. NSCLC A549 cells were treated with MSCs-derived exosomes, after which the migration and invasion of A549 cells were detected and expression of EMT-related proteins (E-cadherin, N-cadherin, and Vimentin), KLF7, p-AKT/AKT, and HIFresults of gain-and loss-of-function assays revealed that miR-204 overexpression in MSCs-derived exosomes inhibited KLF7 expression and the AKT/HIF-impaired cell migration, invasion, as well as EMT. In conclusion, the key findings of the current study demonstrate that exosomal miR-204 from MSCs possesses anticarcinogenic properties against NSCLC via the KLF7/AKT/HIF-

MicroRNA-631 deriving from bone marrow mesenchymal stem cell exosomes facilitates the malignant behavior of non-small cell lung cancer via modulating the E2F family of transcription factor 2/phosphatidylinositol 3‐kinase/Akt signaling pathway

“…MiR-204 [ 33 ], miR-193a [ 5 ] and miR-144 [ 10 ] are included in these miRNAs. The data from this study further complement and support the role of Exo in delivering miRNA [ 34 ].…”

Clinical Roles of Risk Model Based on Differentially Expressed Genes in Mesenchymal Stem Cells in Prognosis and Immunity of Non-small Cell Lung Cancer

“…Several studies have confirmed the importance of the biological functions of MSCs in the progression of NSCLC (Fregni et al, 2018;Gu et al, 2020;Liang et al, 2020;Liu et al, 2021;Yin et al, 2021). MSCs are known to cause transcriptional changes in lung cancer cells, leading to increased expression of MMP9.…”

“…In the TME, MSCs participate in material transportation and intercellular information transmission by secreting exosomes, and regulate tumor cell viability ( Liu et al, 2021 ; Mohr et al, 2021 ; Wang W. et al, 2021 ; Muralikumar et al, 2021 ; Yin et al, 2021 ). Co-culturing MSCs with pancreatic cancer cells shows enhanced expression of metastatic cytokines CCL2 and IL6, which are produced by the stem cells.…”

“…Exosomes of MSCs promote the migration and invasion of NSCLC A549 cells, and enhance the expression of epithelial-mesenchymal transition (EMT) proteins, such as E-cadherin, N-cadherin, Vimentin, KLF7, p -AKT/AKT, and HIF-1α. Overexpression of miR-204 in the exosomes of MSCs inhibits KLF7 expression and AKT/HIF-1α pathway activity, leading to cell migration and invasion ( Liu et al, 2021 ).…”

“…MSCs play an important role in the progression of NSCLC ( Liu et al, 2021 ). However, the mechanisms by which MSCs contribute to the progression of NSCLC have not yet been fully elucidated.…”