The role of exosomal long non-coding RNAs in cancer drug resistance

Abstract

One of the major challenges in oncology is drug resistance, which triggers relapse and shortens patients' survival. In order to promote drug desensitization, cancer cells require the establishment of an ideal tumor microenvironment that accomplishes specific conditions. To achieve this objective, cellular communication is a key factor. Classically, cells were believed to restrictively communicate by ligand-receptor binding, physical cell-to-cell interactions and synapses. Nevertheless, the crosstalk between tumor cells and stroma cells has also been recently reported to be mediated through exosomes, the smallest extracellular vesicles, which transport a plethora of functionally active molecules, such as: proteins, lipids, messenger RNA, DNA, microRNA or long non-coding RNA (lncRNAs). LncRNAs are RNA molecules greater than 200 base pairs that are deregulated in cancer and other diseases. Exosomal lncRNAs are highly stable and can be found in several body fluids, being considered potential biomarkers for tumor liquid biopsy. Exosomal lncRNAs promote angiogenesis, cell proliferation and drug resistance. The role of exosomal lncRNAs in drug resistance affects the main treatment strategies in oncology: chemotherapy, targeted therapy, hormone therapy and immunotherapy. Overall, knowing the molecular mechanisms by which exosomal lncRNA induce pharmacologic resistance could improve further drug development and identify drug resistance biomarkers.

Integrated Transcriptome Analysis of Human Visceral Adipocytes Unravels Dysregulated microRNA-Long Non-coding RNA-mRNA Networks in Obesity and Colorectal Cancer

“…Among adipocytes products that could sustain cancer cell growth, circulating miRNAs, both naked or associated to exosomes, may regulate the function of the immune system and distant organs and could potentially be used as biomarkers of diagnosis and prognosis of obesity and cancer (15). Likewise, exosomal lncRNAs have been shown to promote angiogenesis, cell proliferation and drug resistance and can be found in several body fluids, being highly stable, thus considered potential tumor biomarkers (95).…”

lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System

“…In this review, we gave a comprehensive overview of lncRNAs and their involvement in drug resistance in cancers of the genitourinary system. Understanding the relation between lncRNAs and the biomarkers use and the development of drug and therapy resistance is crucial as lncRNAs may represent powerful therapeutic targets to overcome drug resistance and improve the outcome of cancer patients [206][207][208][209].…”

Extracellular vesicle‐mediated regulation of tumor angiogenesis— implications for anti‐angiogenesis therapy

“…Tumour microenvironment including EVs is revealed to play an essential part in drug resistance. Emerging evidence shows that the mechanisms to induce drug‐resistant phenotypes through EVs are the protein transfer and transmission of nucleic acids 21 . Therefore, blocking tumour angiogenesis signals by controlling of EV secretion or alteration of EV contents may act as a novel strategy to promote the long‐term efficacy of anti‐angiogenic therapies 83 …”