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Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells

ABSTRACT: Analysis of PIWIL1 function in COLO205 [ATCC® CCL-222] colon adenocarcinoma cancer cell culture model.

ORGANISM(S): Homo sapiens

PROVIDER: GSE128526 | GEO | 2019/05/08

REPOSITORIES: GEO

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Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells.

Project description:Germline genes that are aberrantly expressed in nongermline cancer cells have the potential to be ideal targets for diagnosis and therapy due to their restricted physiological expression, their broad reactivation in various cancer types, and their immunogenic properties. Among such cancer/testis genes, components of the PIWI-interacting small RNA (piRNA) pathway are of particular interest, as they control mobile genetic elements (transposons) in germ cells and thus hold great potential to counteract genome instability in cancer. Here, we systematically investigate the potential reactivation of functional piRNA-silencing mechanisms in the aberrant context. While we observe expression of individual piRNA-pathway genes in cancer, we fail to detect the formation of functional piRNA-silencing complexes. Accordingly, the expression of a PIWI protein alone remains inconsequential to the cancer cell transcriptome. Our data provide a framework for the investigation of complex aberrant gene-expression signatures and establish that reactivation of piRNA silencing, if at all, is not a prevalent phenomenon in cancer cells.

| S-EPMC6561285 | biostudies-literature

Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells

Project description:Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells

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piRNA pathway is essential for generating functional oocytes in golden hamster

Project description:Piwi-interacting RNAs (piRNAs) are small RNAs predominantly expressed in germ cells that function in gametogenesis in various species. Notably, PIWI-deficient female mice are fertile and mouse oocytes express a panel of small RNAs that do not appear widely representative of mammals. Thus, the function of piRNAs in mammalian oogenesis remains largely elusive. Here, we generated PIWIL1- and MOV10L1-deficient golden hamsters and found that all female and male mutants were sterile, with severe defects in embryogenesis and spermatogenesis, respectively. PIWIL1-deficient oocytes displayed aberrant transposon accumulation and broad transcriptomic dysregulation, and maternal PIWIL1-deficient embryos had impaired zygotic genome activation (ZGA). Moreover, our results support that PIWIL1-piRNAs exert a non-redundant function in silencing endogenous retroviruses (ERVs) in oocytes. Together, our findings demonstrate that piRNAs are indispensable for generating functional germ cells in golden hamsters and show the informative value of this model species for functional and mechanistic investigations of piRNAs in gametogenesis, especially those related to female infertility.

2021-08-02 | GSE169528 | GEO

RNA-Immunoprecipitation of PIWIL1/piRNA complexes in COLO 205 cells and deep-sequencing of associated small RNAs with NGS technologies

Project description:To evaluate PIWIL1/piRNAs association in the metastatic COLO 205 cell line, we performed an RNA-immunoprecipitation experiment followed by small RNA deep-sequencing (RIP-Seq). For the identification of PIWIL1/piRNA complexes, independent reactions were carried out with two different antibodies (IP1 and IP2); non-specific interactions were computationally filtered out using a No Antibody control (No Ab).

2020-08-05 | E-MTAB-8121 | biostudies-arrayexpress

Homo sapiens strain:ATCC CCL-243

Project description:Human ATCC CCL-243 transcriptome

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Genome-wide profiling of H3K27ac (ChIP-seq) in IMR90 cells

Project description:To determine the genome-wide pattern of H3K27ac in IMR90 (ATCC CCL-186) cells we performed ChIP-seq upon hormone treatment (1.5 h, 1 M dexamethasone).

2018-04-12 | E-MTAB-5355 | biostudies-arrayexpress

RRBS DNA methylation data of bovine embryonic fibroblast cells

Project description:We investigated the effects of one carbon metabolites supplementation on early embryonic development. To this end, the Bovine Embryonic Tracheal Fibroblast cell lines (EBTr; NBL-4; ATCC CCL-44) were cultured under different levels of glucose and OCM (folic acid, choline chloride, vitamin B12, and L-methionine).

2022-03-24 | GSE180362 | GEO

The NMD endonuclease SMG6 co-operates with the piRNA pathway in germ granules to shape the male germ cell transcriptome

Project description:Nonsense-mediated RNA decay (NMD) is a conserved RNA turnover pathway. Here we report that the sole endonuclease in the NMD pathway, SMG6, is essential for the male germline. Germ-cell conditional knockout (cKO) of Smg6 causes complete arrest of spermatogenesis at the early haploid cell stage. Smg6-cKO round spermatids accumulate NMD target mRNAs with long 3’ untranslated regions (UTRs) and fail to eliminate transcripts normally expressed during meiosis, the previous step in spermatogenesis. SMG6 and PIWI-interacting (pi) RNA pathway components are highly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells. This led to the intriguing possibility that the CB is a site where SMG6 and the piRNA pathway co-operate to regulate RNA metabolism. Several findings supported this hypothesis: (i) SMG6 and the piRNA-binding protein PIWIL1 have almost identical temporal expression and localization patterns, (ii) SMG6 and PIWIL1 physically interact, (iii) scores of genes upregulated in Smg6-cKO round spermatids overlap with those upregulated in Piwil1-KO round spermatids, and (iv) the phenotypic defects caused by SMG6 loss phenocopies the defects caused by PIWIL1 loss. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility.

2022-09-27 | GSE182518 | GEO

Expression profiles of genes central to tumour metastasis in human triple-negative breast cancer cells

Project description:Immortalized human breast cancer cell lines, MDA-MB-231(ATCC® HTB-26™) and MDA-MB-468(ATCC® HTB-132™), were analyzed via RT-qPCR for transcript expression of several classes of protein factors including cell adhesion, ECM components, cell cycle, cell growth and proliferation, apoptosis, transcription factors and regulators and other genes related to tumor metastasis.

2016-12-28 | GSE92941 | GEO

piRNA-independent Function of PIWIL1 as a Novel co-activator for Anaphase Promoting Complex/Cyclosome (APC/C) to Drive Pancreatic Cancer Metastasis

Project description:Piwi proteins are normally restricted in germ cells to suppress transposons through association with piRNAs, but are also frequently activated in many types of human cancers. Of great puzzle is the lack of induction of corresponding piRNAs in cancer cells, as we document here in human pancreatic ductal adenocarcinomas (PDAC), implying that such germline-specific proteins are somehow hijacked to promote tumorigenesis through different mode of action. To pursue the underlying mechanism, we now demonstrate that in the absence of piRNAs, the aberrantly induced human PIWIL1 in PDAC functions as an oncoprotein by activating the Anaphase Promoting Complex/Cyclosome (APC/C), which then targets a critical cell adhesion-related protein Pinin to enhance PDAC metastasis. This is in contrast to piRNA-dependent PIWIL1 ubiquitination and removal by APC/C during late spermiogenesis. These findings thus unveil an piRNA-dependent mechanism to switch PIWIL1 from a substrate in spermatids to a co-activator of APC/C in human cancer cells.

2020-02-01 | GSE141340 | GEO

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