Apelin enhances biological functions in lung cancer A549 cells by downregulating exosomal miR-15a-5p

Abstract

Apelin acts as a tumor promoter in multiple malignant tumors; however, its regulatory mechanism remains unclear. Previous studies have indicated that exosomes are pivotal to mediating tumor progression and metastasis. This study examined whether apelin enhances proliferation and invasion ability of lung cancer cells via exosomal miRNA. Lung cancer A549 cells overexpressing apelin and control vector were generated by lentiviral transfection. Exosomes were isolated from the culture supernatant of each cell group, and characterized. A-exo and V-exo were respectively co-cultured with A549 cells, and assays of proliferation, apoptosis, colony formation, and invasion were conducted. Exosomal microRNA (miRNA) sequencing (miRNA-seq) was performed on A-exo and V-exo to select a candidate miRNA. It was found that A549 cells absorbed more A-exo than V-exo, and A-exo could promote proliferation, colony formation, migration and invasion of A549 cells more than V-exo. Exosomal miRNA-seq data revealed that miR-15a-5p was markedly lower in A-exo compared with V-exo. Low expression of miR-15a-5p was also found in lung cancer tissues and cell lines, suggesting that miR-15a-5p may have an anti-tumor role. Overexpression of miR-15a-5p in A549 cells was associated with less cell proliferation, migration, invasion, and suppressed cell cycle; and lower amounts of CDCA4 (cell division cycle-associated protein 4) indicated that it may be a potential target for miR-15a-5p. This study elucidated a novel regulatory mechanism that apelin may promote proliferation and invasion of lung cancer cells by inhibiting miR-15a-5p encapsulated in exosomes.

The Role of TAMs in Tumor Microenvironment and New Research Progress

“…Scavenger receptors CD163 and CD206, as cell surface markers, are highly expressed in M2 TAMs and are considered to be useful for distinguishing M2 phenotype from other M1 phenotype macrophages [28,29]. Notch signal transduction pathway, as a highly conservative signal transduction pathway, involves many cell biological processes including proliferation, angiogenesis, hypoxia, tumor stem cell activity, and epithelial-mesenchymal transformation (EMT), and can also be involved in inducing TAMs polarization [30][31][32]. The ligand of TLR (such as LPS or IFN-γ) can induce macrophages to polarize into M1 phenotype, promote inflammatory reaction, and kill tumor cells.…”

Study Progression of Apelin/APJ Signaling and Apela in Different Types of Cancer

“…Yang et al found that apelin-13 could promote lung adenocarcinoma cell proliferation and induced cell autophagy via extracellular signal-regulated kinases (ERK) 1/2 signaling (36). Ran et al discovered that apelin could promote lung cancer A549 cells proliferation and invasion by inhibiting exosomal miR-15a-5p (37). Interestingly, a recent study revealed that miR-195 could directly target apelin, thus inhibiting lung adenocarcinoma cell proliferation and invasion (38).…”

Identification of key molecules and significant signaling pathways in HNRNPK regulated lung cancer cells

“…The results showed that the "Apelin signaling pathway", and "Oxytocin signaling pathway" were the main changed biological processes by analyzing the KEGG and GO pro les. Similarly, Jingjing Ran et al found that Aplin promotes biological functions in lung cancer cells by inhibiting exosome miR-15a-5p 17 . C Péqueux et al found that Oxytocin promotes the growth of human small-cell lung cancer, which is controlled by the mitogen-activated protein kinase pathway 18 .…”