Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to let-7c-5p and miR-181b-5p.

As carriers containing abundant biological information, exosomes could deliver the property of donor cells to recipient cells. Emerging studies have shown that tumor cells could secrete a mass of exosomes into the microenvironment to regulate bystander cells. However, the underlying mechanisms of such a phenomenon remain largely unexplored. In this research, we purified and identified the exosomes of A549 cells and found that A549-cell-derived exosomes promoted BEAS-2B cells migration, invasion, and epithelial-mesenchymal transition (EMT). Importantly, we observed that let-7c-5p and miR-181b-5p were attenuated in A549-cell-derived exosomes compared to BEAS-2B-cell-derived exosomes. The analysis of miRNA expression level in BEAS-2B cells indicated that incubation with A549-cell-derived exosomes reduced the expression levels of let-7c-5p and miR-181b-5p. In transient transfections assay, we found that downregulation of let-7c-5p and miR-181b-5p simultaneously showed stronger promotion of BEAS-2B cells migration and invasion than individually. Moreover, exosomes secreted from A549 cells with upregulated expression of let-7c-5p and miR-181b-5p significantly reduce their regulatory effect on BEAS-2B cells. Bioinformatics analyses revealed that let-7c-5p and miR-181b-5p inhibit the EMT process mainly by regulating focal adhesion and mitogen-activated protein kinase (MAPK) signaling pathway. Thus, our data demonstrated that A549-cell-derived exosomal let-7c-5p and miR-181b-5p could induce migration, invasion, and EMT in BEAS-2B cells, which might be regulated through focal adhesion and MAPK signaling pathway. The expression level of let-7c-5p and miR-181b-5p may show great significance for the early diagnosis of lung cancer.

The Biological Functions and Clinical Applications of Integrins in Cancers.

Integrins are the adhesion molecules and receptors of extracellular matrix (ECM). They mediate the interactions between cells-cells and cells-ECM. The crosstalk between cancer cells and their microenvironment triggers a variety of critical signaling cues and promotes the malignant phenotype of cancer. As a type of transmembrane protein, integrin-mediated cell adhesion is essential in regulating various biological functions of cancer cells. Recent evidence has shown that integrins present on tumor cells or tumor-associated stromal cells are involved in ECM remodeling, and as mechanotransducers sensing changes in the biophysical properties of the ECM, which contribute to cancer metastasis, stemness and drug resistance. In this review, we outline the mechanism of integrin-mediated effects on biological changes of cancers and highlight the current status of clinical treatments by targeting integrins.

The Role of Exosomal microRNA in Cancer Drug Resistance.

Exosomes affect the initiation and progression of cancers. In the tumor microenvironment, not only cancer cells, but also fibroblasts and immunocytes secrete exosomes. Exosomes act as a communicator between cells by transferring different cargos and microRNAs (miRNAs). Drug resistance is one of the critical factors affecting therapeutic effect in the course of cancer treatment. The currently known mechanisms of drug resistance include drug efflux, alterations in drug metabolism, DNA damage repair, alterations of energy programming, cancer stem cells and epigenetic changes. Many studies have shown that miRNA carried by exosomes is closely associated with the development of drug resistance mediated by the above-mentioned mechanisms. This review article will discuss how exosomal miRNAs regulate the drug resistance.

Anti-Cancer Effects of Pristimerin and the Mechanisms: A Critical Review.

As a quinonemethide triterpenoid extracted from species of the Celastraceae and Hippocrateaceae, pristimerin has been shown potent anti-cancer effects. Specifically, it was found that pristimerin can affect many tumor-related processes, such as apoptosis, autophagy, migration and invasion, vasculogenesis, and drug resistance. Various molecular targets or signaling pathways are also involved, such as cyclins, reactive oxygen species (ROS), microRNA, nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and PI3K/AKT/mammalian target of rapamycin (mTOR) pathways. In this review, we will focus on the research about pristimerin-induced anti-cancer activities to achieve a deeper understanding of the targets and mechanisms, which offer evidences suggesting that pristimerin can be a potent anti-cancer drug.