Abstract
PIWI-interacting RNA (piRNA) is a kind of non-coding single stranded RNA which plays major roles in epigenetic expressions, genome rearrangement, and regulation of gene and protein. Because piRNAs are abnormally expressed in various cancers, they can be used as novel biomarkers and therapeutic targets. However, the roles of piRNAs in cancer cell growth and survival are not well-known. Here, we are the first to provide evidence that PIWI-interacting RNA-004800 (piR-004800) is overexpressed in both exosomes from multiple myeloma (MM) patients' bone marrow supernatant and primary MM cells. The expression level of piR-004800 is positively correlated with the stages of MM, according to the international staging system (ISS). In MM cell lines, downregulation of piR-004800 induced apoptosis and autophagic cell death. This was accompanied by in vitro and in vivo inhibition of cell proliferation. Our previous study shows that sphingosine-1-phosphate receptor (S1PR) signaling pathway plays a crucial part in MM cell proliferation. In this study, we find that S1PR signaling pathway can regulate the PI3K/Akt/mTOR pathway through control of piR-004800 expressions. Taken together our data supports an oncogenic role for piR-004800 in MM, which sheds insight into a new mechanism that may lead to therapeutic targets in MM, an incurable plasma cell neoplasm.
Highlights
Multiple myeloma (MM) is the second most common hematological malignancy
Analyzing primary MM cells and cell lines compared to bone marrow mononuclear cells from normal donors, we found that piR-004800 expression was significantly higher (Figure 1C)
PiRNA can play both an agonistic and antagonistic role in the development of cancer: the precise outcome is determined by tissue specificity
Summary
As a plasma cell malignancy affecting the bone marrow, MM patients display an average 5-year survival rate of about 50% [1]. Research efforts have begun to explore the relationship between piRNA and tumor piR-004800 Regulated MM Survival development. One piRNA, piRNA823, is shown to play the role in tumor formation by effect on DNA methylation and bone marrow microenvironment [7,8,9]. This suggests a generalizable role for piRNAs in MM pathogenesis yet few have been identified. Expressed in MM, we show that piR-004800 is regulated by an upstream metabolic signaling that is dysregulated in MM, the S1PR signaling pathway
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