Chemoresistance and metastasis are the major challenges for the current ovarian cancer treatment. Understanding the mechanisms of ovarian cancer progression and metastasis is critically important for developing novel therapies. The advances in extracellular vesicles (EVs) research in recent years have attracted extensive attention. EVs contain a variety of proteins, RNAs, DNAs, and metabolites. Accumulating evidence indicates that ovarian cancer cells secrete a large amount of EVs, playing an important role in tumor progression and recurrence. In the microenvironment of ovarian tumor, EVs participate in the information transmission between stromal cells and immune cells, promoting the immune escape of ovarian cancer cells and facilitating cancer metastasis. Here, we review the recent advances of EVs in chemoresistance, mechanisms of metastasis, and immune evasion of ovarian cancer. Furthermore, we also discuss the challenges of EV research and future application of EVs as promising biomarker sources in response to therapy and in therapy-delivery approaches for ovarian cancer patients. 

/pdf/extracellular-vesicles-in-ovarian-cancer-chemoresistance-35pamsck.pdf

Extracellular vesicles in ovarian cancer chemoresistance, metastasis, and immune evasion

BACKGROUND Lung cancer has the first place among cancer-related deaths worldwide and demands novel strategies in the treatment of this life-threatening disorder. The aim of this review is to explore the regulation of epithelial-to-mesenchymal transition (EMT) by long non-coding RNAs (lncRNAs) in lung cancer. INTRODUCTION LncRNAs can be considered as potential factors for targeting in cancer therapy, since they regulate a bunch of biological processes, e.g. cell proliferation, differentiation and apoptosis. The abnormal expression of lncRNAs occurs in different cancer cells. On the other hand, epithelial-to-mesenchymal transition (EMT) is a critical mechanism participating in migration and metastasis of cancer cells. METHODS Different databases, including Google Scholar, Pubmed and Science direct, were searched for collecting articles using keywords such as "LncRNA", "EMT", and "Lung cancer". RESULTS There are tumor-suppressing lncRNAs that can suppress EMT and metastasis of lung cancer cells. Expression of such lncRNAs undergoes down-regulation in lung cancer progression and restoring their expression is of importance in suppressing lung cancer migration. There are tumor- promoting lncRNAs triggering EMT in lung cancer and enhancing their migration. CONCLUSION LncRNAs are potential regulators of EMT in lung cancer, and targeting them, both pharmacologically and genetically, can be of importance in controlling the migration of lung cancer cells.

Crosstalk of long non-coding RNAs and EMT: Searching the missing pieces of an incomplete puzzle for lung cancer therapy.

/pdf/extracellular-vesicles-in-ovarian-cancer-chemoresistance-1iqaugl3.pdf

Disorders of miR-484 expression are observed in cancer, different diseases or pathological states. There is accumulating evidence that miR-484 plays an essential role in the development as well as the regression of different diseases, and miR-484 has been reported as a key regulator of common cancer and non-cancer diseases. The miR-484 targets that have effects on inflammation, apoptosis and mitochondrial function include SMAD7, Fis1, YAP1 and BCL2L13. For cancer, identified targets include VEGFB, VEGFR2, MAP2, MMP14, HNF1A, TUSC5 and KLF12. The effects of miR-484 on these targets have been documented separately. Moreover, miR-484 is typically described as an oncosuppressor, but this claim is simplistic and one-sided. This review will combine relevant basic and clinical studies to find that miR-484 promotes tumorigenesis and metastasis in liver, prostate and lung tissues. It will provide a basis for the possible mechanisms of miR-484 in early tumor diagnosis, prognosis determination, disease assessment, and as a potential therapeutic target for tumors.

/pdf/mir-484-a-potential-biomarker-in-health-and-disease-25zdt61u.pdf

miR-484: A Potential Biomarker in Health and Disease

Ovarian cancer (OC) is one of the deadliest gynecological malignancies worldwide and has a high mortality rate. Its dismal prognosis is closely related to late diagnosis and drug resistance. Exosomes are a novel means of intercellular communication that are involved in the genesis and development of tumors by delivering a variety of biologically active molecules, including proteins, lipids, and nucleic acids. As an important component, noncoding RNAs (ncRNAs) are selectively enriched in exosomes and participate in the regulation of specific aspects of OC development, such as proliferation, invasion, metastasis, angiogenesis, immune escape, and treatment resistance. Therefore, strategies that specifically target exosomal ncRNAs may be attractive therapeutic options. Exosomes are readily available in almost all types of human biological fluids and are biocompatible, making them promising biomarkers of OC as well as targets for therapeutic applications. In this review, we briefly summarize the biology of exosomes, the function of exosomal ncRNAs in OC development, and their potential clinical applications as biomarkers and therapeutic tools. Ideally, exosomal ncRNAs will become increasingly valuable in the diagnosis and treatment of OC in the near future.

Emerging Functions and Clinical Applications of Exosomal ncRNAs in Ovarian Cancer.

Background Ovarian cancer (OC) is one of the most common malignancy worldwide. Emerging evidences have demonstrated that microRNAs (miRNAs) play an important role in regulating the initiation and development of OC. Objective The present study was to explore the clinical significance of serum exosomal miR-484 in OC. Methods A total of 113 OC patients and 60 healthy volunteers were enrolled in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure serum exosomal miR-484 levels in blood samples. Results Our results showed that serum exosomal miR-484 levels were significantly lower in OC patients. Serum exosomal miR-484 was able to discriminate OC cases from controls, with an area under the receiver-operating characteristics (ROC) curve (AUC) of 0.821. Combination of serum exosomal miR-484 with CA-125 showed an elevated AUC of 0.912 in identifying OC patients from controls. Moreover, decreased serum exosomal miR-484 expression was significantly associated with aggressive clinical variables as well as shorter overall survival and progression-free survival. The OC patients with simultaneously low serum exosomal miR-484 expression and high serum CA-125 levels tended to suffer the worst clinical outcomes. The multivariate analysis confirmed that low serum exosomal miR-484 level was an independent indicator. Conclusions Collectively, serum exosomal miR-484 could serve as a reliable and non-invasive marker for predicting the prognosis of OC.

Low serum exosomal miR-484 expression predicts unfavorable prognosis in ovarian cancer.

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Low serum exosomal miR-484 expression predicts unfavorable prognosis in ovarian cancer.