Biological Roles and Clinical Significance of Exosome-Derived Noncoding RNAs in Bladder Cancer

Abstract

Bladder cancer (BCa) is a common heterogeneous urinary system tumor with high malignancy and limited advancement in treatment. Limited understanding of BCa has not contributed to any significant progress in diagnosis or treatment, exploring the mechanisms underlying BCa has become an urgent research focus. Exosomes, a type of extracellular vesicle (EV), have drawn substantial interest for their important roles in mediating intracellular communication. Exosomes shuttle numerous bioactive molecules, and noncoding RNAs (ncRNAs) are among the most numerous. ncRNAs including microRNA, long noncoding RNA, and circular RNA are sorted and packaged into exosomes selectively and transferred into recipient cells to regulate their function. Exosomal ncRNAs are associated with hallmarks of BCa, such as proliferation, apoptosis, epithelial-mesenchymal transition (EMT), cell cycle arrest, lymphangiogenesis, and chemotherapy resistance. Exosomal ncRNAs can also be detected in urine and serum, making them encouraging biomarkers for BCa diagnosis and prognosis. More importantly, exosomes exhibit excellent biocompatibility and potential for diversified applications. The delivery of bioactive substances and drugs into specific cells has become a promising approach for precision therapy for BCa patients. In addition, cancer vaccines have also received increasing attention. In this review, we summarize the current research on the regulatory roles of exosomal ncRNAs in BCa tumorigenesis and progression, as well as their potential clinical value in accelerating the diagnosis and therapy of BCa.

Applications of Exosomes in Diagnosing Muscle Invasive Bladder Cancer

“…Several in vitro studies have described the presence of carcinogenic activity being mediated by exosomes. In vitro exosomes demonstrate cellular communication between cancerous bladder cells and histologically diverse tissue, supporting the proposal of exosome mediated metastasis [ 80 , 81 ]. Carcinogenic exosomes had an increase in unfolded endoplasmic reticulum proteins, which leads to the oxidative stress response mechanism within cells when they are proliferating quickly [ 82 ].…”

Urine exosomes as biomarkers in bladder cancer diagnosis and prognosis: From functional roles to clinical significance

“…Methods of altering exosome biogenesis, delivery or cell uptake could be investigated and potentially used to control the detrimental effects of tumor-derived exosomes. There are currently no studies of therapies targeting cancer-derived exosomes in bladder cancer per se, although studies have suggested that EV-targeting antibodies or antagonists showed therapeutic and chemo-/immuno-sensitizing potentials in breast ( 64 ), pancreatic ( 65 , 66 ) and colorectal ( 67 ) cancers.…”

“…There is also interest in utilizing exosomes as a therapeutic vector. Due to their size, ability to cross biological barriers and autologous nature, exosomes could be packaged with pharmacological drugs or tumor-suppressive RNAs that could alter the phenotype of malignant cells ( 64 ). Early-phase clinical trials testing EV-based cancer therapy have been completed ( 68 , 69 ), confirming their capacity to produce anti-tumor effects in patients, and warrant the feasibility of further large-scale investigations.…”

Blood-based liquid biopsy: insights into early detection, prediction, and treatment monitoring of bladder cancer

“…Additionally, exosomes can be designed to deliver different therapeutic loads, including short interfering RNAs, antisense oligonucleotides, chemotherapeutic agents, and immunomodulators, indicating their potential application in tumor therapy [ 147 ]. In addition to their therapeutic potential, exosome-based liquid biopsies highlight their potential application in early cancer diagnosis, progression, prognosis, and response to therapy [ 153 , 154 ]. Current reviews on BC exosomes focus on miRNAs, lncRNAs, and circRNAs.…”