Long non-coding RNAs harboring miRNA seed regions are enriched in prostate cancer exosomes

Abstract

Long non-coding RNAs (lncRNAs) form the largest transcript class in the human transcriptome. These lncRNA are expressed not only in the cells, but they are also present in the cell-derived extracellular vesicles such as exosomes. The function of these lncRNAs in cancer biology is not entirely clear, but they appear to be modulators of gene expression. In this study, we characterize the expression of lncRNAs in several prostate cancer exosomes and their parental cell lines. We show that certain lncRNAs are enriched in cancer exosomes with the overall expression signatures varying across cell lines. These exosomal lncRNAs are themselves enriched for miRNA seeds with a preference for let-7 family members as well as miR-17, miR-18a, miR-20a, miR-93 and miR-106b. The enrichment of miRNA seed regions in exosomal lncRNAs is matched with a concomitant high expression of the same miRNA. In addition, the exosomal lncRNAs also showed an over representation of RNA binding protein binding motifs. The two most common motifs belonged to ELAVL1 and RBMX. Given the enrichment of miRNA and RBP sites on exosomal lncRNAs, their interplay may suggest a possible function in prostate cancer carcinogenesis.

Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer

“…SChLAP1 may therefore be a favorable biomarker for assessing various treatment options for patients with PCa. Another lncRNA, SAP30L-AS1, was one of the lncRNAs existing in exosomes isolated from four PCa cell lines [18]. The current study is the first study to investigate the expression of SAP30L-AS1.…”

“…So far, every cell that has been studied secretes exosomes. Previous studies have demonstrated that tumor-derived exosomes had higher content of miRNA and lncRNA [18, 32, 48, 49]. It was the first of these studies that indicated that exosomes could transport mRNA, miRNA and angiogenic proteins leading to tumor growth and providing blood-based diagnostic information [47].…”

“…For instance, microRNA-1246, included in exosomes derived from breast cancer cells, promotes cell proliferation, invasion and drug resistance by targeting CCNG2 [17]. SAP30L-AS1 was one of the lncRNAs found in exosomes released from four PCa cell lines [18]. Exosomes are small lipid bilayer cup-shaped membrane vesicles of endocytic origin and with 50-90 nm in diameter [19, 20].…”

Interactions of Melatonin and MicroRNAs

“…In exosomes and ectosomes, miRNAs are typically enriched. One of the reasons is that these vesicles also contain larger RNAs, especially lncRNAs and circular RNAs (circRNAs) that act as miRNA "sponges" by binding a high amount of miRNA molecules [9,13,14].…”

Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

“…The development of future isolation techniques for prostasomes found in biological fluids will let to get better insight in the identification and analysis of the protein, lipid and nucleic acids content of them and the potential utility for the diagnosis and prognosis of prostate cancer. Exosomal miRNAs in prostate cancer miRNAs are expressed not only in cells and present in biological fluids, but can be found also in cell-derived extracellular vesicles such as exosomes [51]. In fact, RNA sequencing analysis of plasma-derived exosomes revealed that miRNAs are the most abundant exosomal RNA species [52].…”