LncRNA LUCRC regulates colorectal cancer cell proliferation and tumorigenesis by targeting endoplasmic reticulum stress response
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ABSTRACT:
PROVIDER: PRJNA561081 | ENA |
REPOSITORIES: ENA
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Project description:Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and is well known for its strong invasiveness, rapid recurrence and poor prognosis. Long non-coding RNAs (lncRNAs) have been shown to be involved in the development of variety types of cancers, including colorectal cancer. Here, through transcriptomic analysis and functional screening, we reported that lncRNA LUCRC (LncRNA Upregulated in Colorectal Cancer) is highly expressed in colorectal tumor samples and is required for colorectal cancer cell proliferation, migration and invasion in cultured cells and tumorigenesis in xenografts. LUCRC was found to regulate target gene expression of unfolded protein response (UPR) in endoplasmic reticulum (ER), such as BIP. The clinical significance of LUCRC is underscored by the specific presence of LUCRC in blood plasma of patients with colorectal cancers. These findings revealed a critical regulator of colorectal cancer development, which might serve as a therapeutic target in colorectal cancer.
2020-02-24 | GSE136040 | GEO
Project description:In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments. Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40) and homologous yeast guided entry of tail-anchored proteins (GET) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay. We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae, and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.
2016-11-30 | GSE85686 | GEO
Project description:Targeting endoplasmic reticulum (ER) stress presents a promising strategy in cancer therapy. We have previously reported that a series of 1,2,4-oxadiazole derivatives induces the degradation of epidermal growth factor receptor and c-Met which are implicated in tumorigenesis. Based on our previous SAR studies, herein, we synthesized EMD37, a novel 1,2,4-oxadiazole derivative, and systematically investigated its anticancer activity.
2023-04-19 | GSE201134 | GEO
Project description:Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and is well known for its strong invasiveness, rapid recurrence, and poor prognosis. Long non-coding RNAs (lncRNAs) have been shown to be involved in the development of various types of cancers, including colorectal cancer. Here, through transcriptomic analysis and functional screening, we reported that lncRNA LUCRC (LncRNA Upregulated in Colorectal Cancer) is highly expressed in colorectal tumor samples and is required for colorectal cancer cell proliferation, migration, and invasion in cultured cells and tumorigenesis in xenografts. LUCRC was found to regulate target gene expression of unfolded protein response (UPR) in endoplasmic reticulum (ER), such as BIP. The clinical significance of LUCRC is underscored by the specific presence of LUCRC in blood plasma of patients with colorectal cancers. These findings revealed a critical regulator of colorectal cancer development, which might serve as a therapeutic target in colorectal cancer.
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2023-03-22 | GSE227609 | GEO
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Project description:We obtained transcriptional profiles of third instar eye imaginal disc nuclei with or without endoplasmic reticulum stress using next generation sequencing (NGS). We employed an isolation of nuclei tagged in specific cell type (INTACT) protocol (Ma and Weake, J. of Vis. Exp., 2014) to label nuclear membranes of GMR-GAL4-expressing cells with EGFP. The experimental group also expressed a mutant allele of the membrane visual protein rhodopsin (Rh-1(G69D)), which is known to cause endoplasmic reticulum stress and initiate Unfolded Protein Response (UPR) signaling. The goal of this study was to characterize the transcriptional changes associated with endoplasmic reticulum stress responses in a commonly used platform, the eye imaginal disc.
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Project description:Acromegaly is a growth hormone (GH) excess pathological condition in humans and is associated with somatic disfigurement and a wide variety of systemic manifestations such as arthritis, neuropathies, carpal tunnel syndrome, reproductive disorders, metabolic disorders, and gastrointestinal complications. Studying the effect of growth hormone (GH) excess at the cellular level could help in understanding the underlying causes of acromegaly complications. In our previous publications, we have shown that excess GH increases DNA damage and impairs DNA repair pathways in somatic cells. In addition, we revealed that excessive GH reduces the number of stem cells and causes premature aging. Exaggerated growth is one of the main features of acromegaly and therefore, in this research, we have focused on protein production and biogenesis in acromegaly and whether excess GH is associated with unfolded protein response (UPR) and endoplasmic reticulum (ER) stress. Acromegaly-associated abnormal growth can be caused by hypertrophy or hyperplasia. Using pathway enrichment analysis of RNA seq data from our Zebrafish Acromegaly Model and Flow Cytometry Analysis, here we show a progressive increase in hepatocyte cell size and enrichment of hypertrophy pathways in the muscle and liver. That was associated with a progressive enrichment of protein production pathways and ribosome biogenesis. Moreover, using GSEA (Gene Set Enrichment Analysis) of acromegaly RNA seq data, here we show that endoplasmic reticulum (ER) stress is an accompanying feature of acromegaly disease. Our model exhibited endoplasmic reticulum (ER) stress in various organs, especially in the brain.
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