MicroRNA 421 induces the formation of high-invasive cell subsets of ovarian cancer from low-invasive cell subsets mediated by exosomes by activating the PI3K/AKT pathway

Abstract

Abstract Background Intra-tumoral heterogeneity (ITH) has resulted in treatment failure of ovarian cancer(OC). Exosomes and microRNA plays a crucial role in the progression of OC. Therefore, we aimed to explore the effect of exosomes and microRNA421 (miR-421), mediated by exosomes, on the ITH by activating the PI3K/AKT pathway and the diagnosis of OC. Method Exosomes derived from AHC/ALC cells (AHE/ALE) were extracted by differential centrifugation. CCK8, 5-ethyl-2'-deoxyridine(EdU), Transwell, Colony formation and Wound healing assays were performed to explore the proliferation, invasion, and migration abilities. Western blot (WB) assay was used to detect the changes in the epithelial-mesenchymal transition (EMT) and PI3K/AKT pathway. Immunofluorescence assay was used to detect changes in EMT. qRT-PCR was used to detect microRNA levels in serum exosomes from high grade serous ovarian cancer (HGSOC) and benign patients. We also measured the levels of CA125 in serum exosomes. Result AHE and miR-421, mediated by exosomes, significantly increased the malignancy of ALC cells by activating the PI3K/AKT pathway. the expression of miR-421 was significantly increased in the serum exosomes derived from HGSOC patients. Receiver operating characteristic (ROC) curve analysis showed that the combination of miR-421, and serum CA125 can significantly improve the specificity of serum CA125 in the diagnosis of HGSOC. Conclusion MiR-421, mediated by exosomes, could induce the transformation of high-invasive cell subpopulations from low-invasive cell subpopulations of OC cells by activating the PI3K/AKT pathway. MiR-421 could serve as a potentially effective therapeutic target and a novel tumor marker for early diagnosis of OC.