Project description:TRA2β4 is transcribed from the human transformer 2β(TRA2B) gene and overexpressed in colon cancer cells. Nucleolin is one of RNA-binding proteins to regulate cell survival and proliferation. In this study, TRA2β4 and Nucleolin levels were reduced in colon cancer HCT116 cells and gene expression levels were measured using microarray analysis.
Project description:To further explore the function and underlying mechanism of nucleolin in embryonic stem cells (ESCs), we compared the transcription profile of tetracycline (Tc)-inducible EGFP (as a control) or nucleolin siRNA expression-stable ESCs cultured with or without Tc for 3 days, and identified distinct classes of up- and down-regulated genes by nucleolin in mouse ESCs. Total RNA obtained from CGR8 ES cells stably integrated with Tc-inducible siRNA EGFP, nucleoin-1 or nucleolin-2 cultured with or without Tc for 3 days, and then hybridized to Illumina Sentrix Mouse-6 v2.0 BeadChips. Three replicates each condition.
Project description:To further explore the function and underlying mechanism of nucleolin in embryonic stem cells (ESCs), we compared the transcription profile of tetracycline (Tc)-inducible EGFP (as a control) or nucleolin siRNA expression-stable ESCs cultured with or without Tc for 3 days, and identified distinct classes of up- and down-regulated genes by nucleolin in mouse ESCs.
Project description:Lamin A/C proteins, major components of the nuclear lamina, are encoded by the LMNA gene. These proteins have multiple cellular functions. LMNA has implications in cancer; however, its mechanisms of dysregulation in cancer cells are not yet fully understood. Among the LMNA transcript variants, we focused on a spliced variant 6 (termed LMNA-V6), which contains unique 3 exons upstream of exon 1 of LMNA. In this study, after LMNA-V6 levels were modulated by overexpression or silencing in colon cancer HCT116 cells, gene expression profiles were measured using microarray analysis.
Project description:Colorectal cancer (CRC) responses to mutant-selective KRAS inhibitors remain modest, with stable disease and rapid recurrence as the most common outcomes. The molecular mechanisms enabling CRC cells to tolerate KRAS inhibition and ultimately develop resistance remain poorly understood. Here, we investigated early transcriptional and proteomic responses to KRAS silencing in 3D CRC cell line spheroid models, aiming to identify pathways associated with sensitivity or resistance to KRAS blockade. Cell lines were stratified into KRAS silencing-sensitive (HCT116 and SW480) and -resistant (LS174T and SW837) groups based on spheroid growth, cell cycle progression, and apoptosis induction. Transcriptional profiling revealed the unfolded protein response (UPR) and WNT/β-catenin signaling as pathways specifically upregulated in KRAS silencing-sensitive cells and downregulated in resistant cells. Proteomic analysis of membrane-enriched fractions further supported UPR deregulation, showing a pronounced downregulation of translation-related proteins in sensitive cells. Functional assays validated that the sensitive cell line HCT116 exhibits reduced protein aggregation and lower translational capacity upon KRAS knockdown, consistent with UPR activation. Pharmacological inhibition of IRE1α-mediated UPR signaling did not revert KRAS silencing-induced cell cycle arrest or apoptosis in this cell line. Collectively, our results highlight the UPR activation as an early adaptive response of KRAS-dependent CRC cells tolerant to KRAS silencing.