Dataset Information

PIWI-Interacting RNA-004800 Is Regulated by S1P Receptor Signaling Pathway to Keep Myeloma Cell Survival.

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.

SUBMITTER: Ma H

PROVIDER: S-EPMC7175921 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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PIWI-Interacting RNA-004800 Is Regulated by S1P Receptor Signaling Pathway to Keep Myeloma Cell Survival.

Ma Huanxin H Wang Huihan H Tian Fei F Zhong Yuan Y Liu Zhuogang Z Liao Aijun A

Frontiers in oncology 20200415

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 bot ...[more]

PMID: 32351883

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Project description:Because sphingosine 1-phosphate (S1P) is a potent stimulator of angiogenesis, we hypothesized that the S1P pathway is activated to stimulate endometrial/placental angiogenesis during pregnancy. We initially localized S1P signaling pathway members in the gravid and nongravid uterine horns of unilaterally pregnant ewes. Sphingosine kinase-1 expression was greater in gravid compared to nongravid horns. In situ hybridization revealed elevated expression of sphingosine 1-phosphate phosphatase (SGPP1) in gravid interplacentomal endometrial stroma on Days 20 and 40 compared to the nongravid uterine horn, but expression increased in endometrium of the nongravid uterine horn between Days 40 and 120. SGPP1 expression increased in placentomes late in gestation. Sphingosine 1-phosphate lyase mRNA was modestly expressed at Day 20 and then decreased. In contrast, sphingosine 1-phosphate receptor 1 (S1PR1) mRNA increased in endometrium and caruncular stroma of the gravid uterine horn. Treatment with FTY720 and VPC23019, S1P receptor antagonists, blocked human and ovine endothelial cell invasion using an in vitro model of sprouting angiogenesis. Knockdown of S1PR1 with siRNA reduced invasion responses as well. We previously reported that delta-like 4 (DLL4) and A disintegrin and metalloproteinase with thrombospondin-like repeats 1 (ADAMTS1) participate in endothelial cell invasion stimulated by S1P and growth factors in vitro, and thus investigated whether their expression correlated with areas undergoing angiogenesis in vivo. DLL4 expression was similar to S1PR1, while ADAMTS1 mRNA was expressed by endometria of both nongravid and gravid horns, as well as conceptus and placentomes. These results establish that S1P signaling pathway members and S1P- and growth factor-regulated genes are prominent in uterine and placental tissue and in some cases are correlated with areas undergoing angiogenesis. Thus, S1P signaling may be crucial for proper fetal-placental development.

Project description:PIWI-interacting RNAs (piRNAs) are a novel class of small ncRNAs initially isolated from germ line cells; although recent studies report that they are expressed also in somatic cells. To elucidate the role of piRNAs in somatic cells, in particular from breast cancer, we performed the first extensive next generation sequencing expression analysis of small RNA transcriptomes of hormone responsive breast cancer cell lines in different culture conditions. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GSE39162) database was used. Results led to the identification of ~100 and ~150 human piRNAs in the breast cancerous cell lines and tumors respectively, several of which differentially expressed in cell lines under different experimental conditions tested or in response to ERβ and in tumor tissues. Western blotting and Q-PCR analysis also revealed the presence in breast cell lines of PIWIL (PIWI Like) subfamily members proteins encoded in the human genome (PIWIL2/HILI and PIWIL4/HIWI2) and of other components of the piRNA biogenesis pathways, suggesting that this might indeed be functional in somatic cells. These results show that piRNAs are expressed in human somatic cells, in particular in cancer, where their expression is influenced by neoplastic transformation, growth conditions and estrogen receptor beta. More important, we demonstrate for the first time a distinct pattern of piRNAs expression in cancerous vs normal breast tissues, which suggests a potential role of these epigenetic modulators in mammary carcinogenesis and maintenance of the cancer cell phenotype. In addition, to understand the behavior of piRNAs with respect to miRNAs in breast tumor tissues, small RNA sequence data set available in Gene Expression Omnibus (GEO; GSM957192 TAX577740T ,GSM957194 TAX577740N, GSM957195 TAX577453T, GSM957197 TAX577453N, GSM957198 TAX577745T, GSM957200 TAX577745N, GSM957201 TAX577579T, GSM957203 TAX577579N) was used.

Dataset Information

PIWI-Interacting RNA-004800 Is Regulated by S1P Receptor Signaling Pathway to Keep Myeloma Cell Survival.

Publications

PIWI-Interacting RNA-004800 Is Regulated by S1P Receptor Signaling Pathway to Keep Myeloma Cell Survival.

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