Abstract
Extracellular vesicles (EVs) play crucial roles in intercellular communication. miRNAs derived from EVs emerge as promising diagnostic indicators and therapeutic targets in a variety of malignancies. Tremendous studies have revealed the function of miRNAs derived from EVs in tumorigenesis, metastasis and other aspects. The mechanism of action of EV-derived miRNAs, however, in ovarian cancer remains largely unknown. In this study, EVs were enriched from the ovarian cancer cell lines. EVs as a whole could promote cell proliferation, invasion and new vasculature formation. However, the down-regulated EV-derived miR-320a was demonstrated to potentially suppress tumorigenesis, metastasis and angiogenesis. Moreover, EV-derived miR-320a has been proved to directly regulate a previously unknown target, ZC3H12B. An unreported role of ZC3H12B in promoting ovarian cancer cell proliferation has been elucidated and miR-320a could mediate the expression of ZC3H12B, thereby inhibiting the downstream response. As for the practical clinic values, lower expression of EV-derived miR-320a correlates with shorter survival period, indicating that EV-derived miR-320a may also serve as a prognostic biomarker in ovarian cancer. This research provides new insight into the molecular mechanism of EV-derived miR-320a in ovarian cancer and may provide new therapeutic and prognostic strategies for ovarian cancer treatment.
Highlights
Regardless of the development of new remedies in cancer treatment, ovarian cancer (OC) remains one of the leading causes of the malignancies in female cancer patients with high relapse rate
Nanoparticle tracking analysis (NTA) was utilized to measure the size and the concentration of Extracellular vesicles (EVs), a conventional approach based on the tracking of Brownian movement [26]
The cell communication is mediated by EVs secreted by various types of cells [27]
Summary
Regardless of the development of new remedies in cancer treatment, ovarian cancer (OC) remains one of the leading causes of the malignancies in female cancer patients with high relapse rate. A high proportion (59%) of patients diagnosed already have distant metastases. The 5-year survival rate is 48% overall. For those with OC at advanced stage, the rate drops to 29%, compared to 92% for primary disease [1]. Great obstacles for improving the prognosis of OC patients include lack of specific and sensitive diagnostic indicators as well as precision therapeutic options based on the tumor. Yan Huang and Midie Xu contributed to this work
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