Enrichment of Human Stem-Like Prostate Cells with s-SHIP Promoter Activity Uncovers a Role in Stemness for the Long Noncoding RNA <i>H19</i>

Roy, Hélène Bauderlique‐Le; Vennin, Constance; Brocqueville, Guillaume; Spruyt, Nathalie; Adriaenssens, Éric; Bourette, Roland P.

doi:10.1089/scd.2014.0386

Cited by 46 publications

(35 citation statements)

References 57 publications

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“…Furthermore, a recent study of prostate and breast human cell lines revealed a putative role of stemness for H19 , since its expression was positively correlated with stem cells markers and pluripotency factors. H19 was also found to control the expression of two major pluripotency factors, Oct4 and Sox2, which apparently regulate H19 in an amplification feedback loop [ 87 ].…”

Section: H19 In Emtmentioning

confidence: 99%

The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory

et al. 2015

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The imprinted oncofetal long non-coding RNA (lncRNA) H19 is expressed in the embryo, down-regulated at birth and then reappears in tumors. Its role in tumor initiation and progression has long been a subject of controversy, although accumulating data suggest that H19 is one of the major genes in cancer. It is actively involved in all stages of tumorigenesis and is expressed in almost every human cancer. In this review we delineate the various functions of H19 during the different stages in the complex process of tumor progression. H19 up-regulation allows cells to enter a “selfish” survival mode in response to stress conditions, such as destabilization of the genome and hypoxia, by accelerating their proliferation rate and increasing overall cellular resistance to stress. This response is tightly correlated with nullification, dysfunction or significant down-regulation of the master tumor suppressor gene P53. The growing evidence of H19’s involvement in both proliferation and differentiation processes, together with its involvement in epithelial to mesenchymal transition (EMT) and also mesenchymal to epithelial transition (MET), has led us to conclude that some of the recent disputes and discrepancies arising from current research findings can be resolved from a viewpoint supporting the oncogenic properties of H19. According to a holistic approach, the versatile, seemingly contradictory functions of H19 are essential to, and differentially harnessed by, the tumor cell depending on its context within the process of tumor progression.

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Section: H19 In Emtmentioning

confidence: 99%

The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory

et al. 2015

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“…H19 expression has been shown to positively correlate with the level of stem cell genes and pluripotency factors in various tumor types (Bauderlique‐Le Roy et al , 2015; Li et al , 2016; Peng et al , 2017; Zeira et al , 2015). Comparison of the PIM‐i‐resistant (SUP‐T1 and CUTLL1) and PIM‐i‐sensitive (HSB‐2 and DU.528) T‐ALL cell lines revealed significantly elevated SOX2 expression in sensitive vs resistant T‐ALL cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

PIM protein kinases regulate the level of the long noncoding RNA H19 to control stem cell gene transcription and modulate tumor growth

et al. 2020

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The proviral integration site for Moloney murine leukemia virus (PIM) serine/threonine kinases have an oncogenic and prosurvival role in hematological and solid cancers. However, the mechanism by which these kinases drive tumor growth has not been completely elucidated. To determine the genes controlled by these protein kinases, we carried out a microarray analysis in T‐cell acute lymphoblastic leukemia (T‐ALL) comparing early progenitor (ETP‐ALL) cell lines whose growth is driven by PIM kinases to more mature T‐ALL cells that have low PIM levels. This analysis demonstrated that the long noncoding RNA (lncRNA) H19 was associated with increased PIM levels in ETP‐ALL. Overexpression or knockdown of PIM in these T‐ALL cell lines controlled the level of H19 and regulated the methylation of the H19 promoter, suggesting a mechanism by which PIM controls H19 transcription. In these T‐ALL cells, the expression of PIM1 induced stem cell gene expression (SOX2, OCT‐4, and NANOG) through H19. Identical results were found in prostate cancer (PCa) cell lines where PIM kinases drive cancer growth, and both H19 and stem cell gene levels. Small molecule pan‐PIM inhibitors (PIM‐i) currently in clinical trials reduced H19 expression in both of these tumor types. Importantly, the knockdown of H19 blocked the ability of PIM to induce stem cell genes in T‐ALL cells, suggesting a novel signal transduction cascade. In PCa, increases in SOX2 levels have been shown to cause both resistance to the androgen deprivation therapy (ADT) and the induction of neuroendocrine PCa, a highly metastatic form of this disease. Treatment of PCa cells with a small molecule pan‐PIM‐i reduced stem cell gene transcription and enhanced ADT, while overexpression of H19 suppressed the ability of pan‐PIM‐i to regulate hormone blockade. Together, these results demonstrate that the PIM kinases control the level of lncRNA H19, which in turn modifies stem cell gene transcription regulating tumor growth.

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“…We have previously shown that s-SHIP-GFP promoter reporter tracks subset of human prostate RWPE-1 cells enriched in stem cell characteristics [ 45 ]. s-SHIP is also expressed in numerous cancer cell lines and xenograft–maintained human prostate cancers ( Supplementary Figure 3A ) which represent relevant models of prostate cancer [ 46 – 48 ].…”

Section: Discussionmentioning

confidence: 99%

s-SHIP expression identifies a subset of murine basal prostate cells as neonatal stem cells

et al. 2016

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Isolation of prostate stem cells (PSCs) is crucial for understanding their biology during normal development and tumorigenesis. In this aim, we used a transgenic mouse model expressing GFP from the stem cell-specific s-SHIP promoter to mark putative stem cells during postnatal prostate development. Here we show that cells identified by GFP expression are present transiently during early prostate development and localize to the basal cell layer of the epithelium. These prostate GFP+ cells are a subpopulation of the Lin− CD24+ Sca-1+ CD49f+ cells and are capable of self-renewal together with enhanced growth potential in sphere-forming assay in vitro, a phenotype consistent with that of a PSC population. Transplantation assays of prostate GFP+ cells demonstrate reconstitution of prostate ducts containing both basal and luminal cells in renal grafts. Altogether, these results demonstrate that s-SHIP promoter expression is a new marker for neonatal basal prostate cells exhibiting stem cell properties that enables PSCs in situ identification and isolation via a single consistent parameter. Transcriptional profiling of these GFP+ neonatal stem cells showed an increased expression of several components of the Wnt signaling pathway. It also identified stem cell regulators with potential applications for further analyses of normal and cancer stem cells.

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Enrichment of Human Stem-Like Prostate Cells with s-SHIP Promoter Activity Uncovers a Role in Stemness for the Long Noncoding RNA H19

Cited by 46 publications

References 57 publications

The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory

The H19 Long non-coding RNA in cancer initiation, progression and metastasis – a proposed unifying theory

PIM protein kinases regulate the level of the long noncoding RNA H19 to control stem cell gene transcription and modulate tumor growth

s-SHIP expression identifies a subset of murine basal prostate cells as neonatal stem cells

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