Microparticle conferred microRNA profiles - implications in the transfer and dominance of cancer traits

Abstract

BackgroundMicroparticles (MPs) are membrane vesicles which are released from normal and malignant cells following a process of budding and detachment from donor cells. MPs contain surface antigens, proteins and genetic material and serve as vectors of intercellular communication. MPs comprise the major source of systemic RNA including microRNA (miRNA), the aberrant expression of which appears to be associated with stage, progression and spread of many cancers. Our previous study showed that MPs carry both transcripts and miRNAs associated with the acquisition of multidrug resistance in cancer.ResultsHerein, we expand on our previous finding and demonstrate that MPs carry the transcripts of the membrane vesiculation machinery (floppase and scramblase) as well as nucleic acids encoding the enzymes essential for microRNA biogenesis (Drosha, Dicer and Argonaute). We also demonstrate using microarray miRNA profiling analysis, the selective packaging of miRNAs (miR-1228*, miR-1246, miR-1308, miR-149*, miR-455-3p, miR-638 and miR-923) within the MP cargo upon release from the donor cells.ConclusionsThese miRNAs are present in both haematological and non-haematological cancer cells and are involved in pathways implicated in cancer pathogenesis, membrane vesiculation and cascades regulated by ABC transporters. Our recent findings reinforce our earlier reports that MP transfer ‘re-templates’ recipient cells so as to reflect donor cell traits. We now demonstrate that this process is likely to occur via a process of selective packaging of nucleic acid species, including regulatory nucleic acids upon MP vesiculation. These findings have significant implications in understanding the cellular basis governing the intercellular acquisition and dominance of deleterious traits in cancers.

Enigmatic Exosomes: Role in health and disease with significance in cancer

“…In contrast, the exosomal microRNA content was found to be similar to that in the original tumor, thus giving the idea of their possible use as diagnostic marker [12]. However, an abundance of certain micro RNAs that are absent or present at very low levels in the parental cells has recently been noticed [101,102]. These shows that some microRNAs may be preferentially released.…”

Selective surface marker and miRNA profiles of CD34+ blast-derived microvesicles in chronic myelogenous leukemia

“…For example, miR-638 may be stably detected in human plasma, and the miR-92/miR-638 ratio in plasma may be a useful indicator to distinguish between patients with leukemia and the healthy control group (27). Jaiswal et al (28) identified that miR-1246, miR-1308, miR-638 and other human miRNAs may be selectively enriched in microparticles, transferring them to the recipient cells. Similarly, the results of the present study identified that MVs, which cannot be distinguished from microparticles at present, package miR-638.…”

The network of P-glycoprotein and microRNAs interactions

“…147 miR-455-3p has been related to P-gp levels in human ALL cell lines by mechanisms not fully understood, as will be referred in "P-gp and the microRNAs Involved in its Regulation May Be Present in Microvesicles and Exosomes, and May Be Transferred Between Cells" below. 148 …”

“…160 Other recent work also demonstrated that some miRs that are shed from microvesicles play an important role in MDR. 148 The authors observed that one of the significantly expressed and shed miRs, miR-455-3p, is possibly related to P-gp levels. In this study, results from microarray analysis showed that miR-455-3p was less expressed in a P-gp overexpressing resistant leukemia cell line, when compared with the parental sensitive cell line.…”

“…Moreover, following the transfer of microvesicles from the resistant to the sensitive cell lines, it was observed that the sensitive cells acquired lower miR-455-3p and higher P-gp levels. 148 The mechanisms involved in the regulation of P-gp by this miR are not understood (as previously mentioned in "miRs regulating P-gp through mechanisms of regulation not fully understood" section).…”