CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-ß pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday. Overall design: To analyse the binding targets of miR-432-5p we performed a mRNA pulldown using a synthetic biotin laballed miR-432-5p. RNAseq was performed to identify the captured mRNA.
MicroRNA-Mediated Suppression of the TGF-β Pathway Confers Transmissible and Reversible CDK4/6 Inhibitor Resistance.
Specimen part, Subject
View SamplesImmune interferon beta and gamma are essential for mammalian host defence against intracellular pathogens.
GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8.
Cell line
View SamplesExcessive accumulation of lipids in the adipose tissue is a major problem in the present-day broiler industry. However, few studies have analyzed the expression of adipose tissue genes that are involved in pathways and mechanisms leading to adiposity in chickens. Gene expression profiling of chicken adipose tissue could provide key information about the ontogenesis of fatness and clarify the molecular mechanisms underlying obesity.
Profiling of chicken adipose tissue gene expression by genome array.
Age
View SamplesCutaneous CD30+ lymphoproliferative disorder (CD30+LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (PCALCL), comprises the second most common group of cutaneous T cell lymphoma. Previously, we reported that special AT-rich sequence-binding protein1 (SATB1), a thymocyte specific chromatin organizer, was over-expressed and promoted malignant T-cell proliferation in a portion of CD30+LPDs, whereas other CD30+LPDs didn't express SATB1 at all. To elucidate the underlying molecular events in CD30+LPDs with differential SATB1 expression, we subjected 4 SATB1+ and 3 SATB1- CD30+LPDs skin biopsies to second-generation RNA-sequencing (RNA-seq). These data provide a significant resource for studies of CD30+LPDs. Overall design: 200ng total RNA samples were extracted and purified from 7 CD30+LPDs skin lesions (4 SATB1+, 3 SATB1-) to establish RNA library. Then the library was qualified through Agilent 2100 bioanalyzer instrument (Agilent Technologies, Santa Clara, CA) and Quantitative real-time polymerase chain reaction. The qualified library was sequenced on an Illumina HiSeqTM 2000 platform using paired-end reads. 10G raw data for each sample were obtained. The reads were aligned to the hg19 genome with SOAPaligner/SOAP2. Gene expression levels were calculated by reads per kilobase transcriptome per million mapped reads(RPKM)method.
SATB1 Defines a Subtype of Cutaneous CD30<sup>+</sup> Lymphoproliferative Disorders Associated with a T-Helper 17 Cytokine Profile.
Specimen part, Subject
View SamplesHaploid pluripotent stem cells, such as haploid embryonic stem cells (haESCs), facilitate the genetic study of recessive traits. In vitro, fish haESCs maintain haploidy in both undifferentiated and differentiated states, but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested. Here, we report that mouse haESCs can differentiate in vitro into haploid epiblast stem cells (haEpiSCs), which maintain an intact haploid genome, unlimited self-renewal potential, and durable pluripotency to differentiate into various tissues in vitro and in vivo. Mechanistically, the maintenance of self-renewal potential depends on the Activin/bFGF pathway. We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.
Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro.
Specimen part
View SamplesGlioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with glioma initiating cells (GICs) implicated to be critical for tumor progression and resistance to therapy. KDM1B is involved in regulating GICs'' responses to hypoxia, since over-expression of KDM1B delays the cell growth under hypoxia while knocking-down of KDM1B in GICs promotes their survival and tumorigenic abilities. Overall design: We used RNA-Sequencing to detail the global change of gene expression in GICs with knockdown of KDM1B, and identified de-regulated genes and pathways downstream of KDM1B. CD133+ D456MG GICs were infected with non-targeting control and shRNA of KDM1B. Then RNA was extracted and gene expression was profiled by RNA-Seq.
MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.
No sample metadata fields
View SamplesSolar ultraviolet CUV-Cradiation reaching the Earths surface is little due to the filtering effects of the stratospheric ozone layer. At present, artificial UV-C irradiation is utilized for different biological processes. Grape is a major fruit crop around the world. Research has shown that UV-C irradiation induced the biosynthesis of phenols. However, changes at the molecular level in response to UV-C and leading to these effects are poorly understood. To elucidate the effect of UV-C on expression of genes in grape and the response mechanism, transcript abundance of grape (Vitis vinifera L.) leaves was quantified using the Affymetrix Grape Genome oligonucleotide microarray (15,700 transcripts)
Transcriptomic analysis of grape (Vitis vinifera L.) leaves after exposure to ultraviolet C irradiation.
Age, Treatment
View SamplesAlthough the well-known importance of pig in agriculture, as well as a model for human biology, the miRNA catalog of pig has been largely undefined. Identification and preliminary characterization of adipose- and muscle-specific miRNAs would be a prerequisite for a thorough understanding of their roles in regulating adipose deposition and muscle growth. In the present study, we get insight into the miRNA transcriptome in eight adipose tissues, two skeletal muscles and cardiac muscle of pig using deep sequencing technology, and to elucidate their characteristic tissue-specific profiles and genomic context. Overall design: Eleven small RNA libraries from eight adipose tissues, two skeletal muscle tissues and cardiac muscle of pig were sequenced.
An atlas of DNA methylomes in porcine adipose and muscle tissues.
Sex, Age, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comprehensive molecular and immunological characterization of hepatocellular carcinoma.
Specimen part, Cell line
View SamplesHepatocellular carcinoma (HCC) is a heterogeneous disease with a variety of etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multifocal recurrence. Comprehensive molecular evaluation of HCC by multiplatform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying DNA hypermethylation; and (3) metabolic syndrome-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly discriminated HCC with intrahepatic metastasis (IM) from multicentric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not linked to the IM/MC diagnosis, but rather the integrated classification. Thus, identification of these HCC subtypes provides insights into patient stratification and opportunities for therapeutic development.
Comprehensive molecular and immunological characterization of hepatocellular carcinoma.
Specimen part
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