HT29 cells were transsfected with siRNA (siHX), which is targeting the human endogeous retrovirus HERV-HX. Cells were harvested 72 h after transfection and knock-down of HERV-HX was evaluated by quantitative RT-PCR.
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View SamplesMultiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and re-populate the tumor. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and re-activation. In this study we track individual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state which is switched on by engagement with bone lining cells or osteoblasts, and switched off by osteoclasts remodeling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy targeting dividing cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche.
Specimen part
View SamplesK-RAS activating mutations occur frequently in non-small cell lung cancer (NSCLC), leading to aberrant activation of Ras-MAPK signaling pathway that contributes to the malignant phenotype. However, the development of Ras-targeted therapeutics remains challenging. Here, we show that MED23, a component of the multisubunit Mediator complex that is known to integrate signaling and gene activities, is selectively important for Ras-active lung cancer. By screening a large panel of human lung cancer cell lines with or without a Ras mutation, we found that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity. Med23-deficiency in fibroblasts selectively inhibited the oncogenic transformation induced by Ras but not by c-Myc. Transcription factor ELK1, which is phosphorylated by MAPK for relaying the Ras signaling to MED23, was also required for the Ras-driven oncogenesis. Transcriptiome analysis revealed that MED23 and ELK1 co-regulate a common set of target genes enriched in regulating cell cycle and proliferation to support the Ras-dependency. Furthermore, correlated with the strength of Ras signaling as indicated by the ELK1 phosphorylation level, MED23 was up-regulated by Ras-transformation, and was found to be overexpressed in both Ras-mutated lung cancer cell lines and primary tumor samples. Remarkably, lower Med23 expression predicts better survival in Ras-active lung cancer patients and xenograft mice. Collectively, our findings demonstrate a critical role for MED23 in enabling the Ras-addiction of lung carcinogenesis, thus providing a vulnerable target for the treatment of Ras-active lung cancer.
Selective requirement for Mediator MED23 in Ras-active lung cancer.
Specimen part, Cell line
View SamplesRNA-seq study of tumors that develop in mice after injection of gastric carcinoma cell line, AGS, with or without Epstein-Barr virus infection
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Sex, Specimen part, Disease, Cell line
View SamplesRNA-Seq study of tumors that develop in mice after injection of nasopharyngeal carcinoma (NPC) cell line C666.1 and the xenograph tumors C15 and C17
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Sex, Specimen part, Disease, Cell line
View Samplesthe goal of this study are to reveal potential functions of novel lncRNAs in PDLSCs ,systematicly characterize PDLSC related lncRNAs and protein coding genes in uPDLSCs,dPDLSCs and TNF-a-dPDLSCs with Next Generation Sequencing.
No associated publication
Sex, Specimen part, Treatment
View SamplesSkeletal muscle must perform a wide range of kinds of work, and different fiber types have evolved to accommodate these different tasks. The attributes of fibers are determined in large part by the coordinated regulation of oxidative capacity, as reflected by mitochondrial content, and the specific makeup of myofibrillar proteins. Adult muscle fibers contain four myosin heavy chain isotypes: I, IIa, IIx and IIb. Type I and IIa fibers have slower twitches and are rich in mitochondria, while type IIb fibers are fast-twitch and predominantly glycolytic. The intermediate IIx fibers are less well understood. Previous work had shown that the transcriptional coactivator PGC-1 alpha could drive the formation of type I and IIa muscle fibers. We show here that mice with transgenic expression of PGC-1 beta in skeletal muscle results in marked induction of IIx fibers. The fibers in transgenic mice are rich in mitochondria and are highly oxidative. As a result, PGC-1 beta transgenic animals can perform oxidative activity for longer and at higher work loads than wild type animals. In cell culture, PGC-1 beta coactivates the MEF2 family of transcription factors to stimulate the MHC IIx promoter. Together, these data indicate that PGC-1 beta is sufficient to drive the formation in vivo of highly oxidative fibers with type IIx characteristics.
The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle.
Sex, Specimen part
View SamplesMesenchymal stromal cells (MSCs), which have immunosuppressive and trophic abilities that are induced by inflammatory cytokines, have emerged as a promising option for cell-based therapy. The cytokine profiles vary substantially across different diseases and stages of disease progression, which has been shown to influence the curative properties of MSCs. Our knowledge about how MSCs respond systemically to cytokines is still limited. Here, we individually stimulated MSCs in vitro with IFN-?and used RNA-Seq to analyze their expression profiles.
No associated publication
Sex, Specimen part
View SamplesWe used microarrays to detail the gene expression profiles of KYSE170 cell line to identify distinct up and down-regulated genes during treatment with ethyl-3,4-dihydroxybenzoate.
No associated publication
Cell line, Treatment
View SamplesWe used microarrays to detail the gene expression profiles of KYSE410 cell line to identify distinct up and down-regulated genes during treatment with cisplatin.
No associated publication
Cell line, Treatment
View Samples