The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway
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PROVIDER: PRJNA1029580 | ENA |
REPOSITORIES: ENA
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Project description:Glioma is the most common and aggressive primary malignant brain tumor. N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. Here, we show that the m6A reader HNRNPC was overexpression and related to poor prognosis in glioma patients. HNRNPC plays crucial role in glioma cell proliferation, invasion and tumorigenesis. HNRNPC augments m6A-dependent mRNA stability of IRAK1, which impacted poor survival for glioma patients, further activated the downstream MAPK pathway. HNRNPC promotes glioma cells progression largely through the upregulation of IRAK1. Together, our findings demonstrate the novel HNRNPC-IRAK1-MAPK axis critical for glioma tumorigenesis and extend the reason for the upregulation of IRAK1.
2024-06-12 | GSE245688 | GEO
Project description:HNRNPC, as one of the m6A reading proteins, has been confirmed to be highly expressed in a variety of tumors and promote the occurrence and progression of tumors. Previous studies have confirmed that HNRNPC significantly promoted the proliferation, migration and invasion of NSCLC cells, and its high expression was related to the clinical stage, lymph node and distant metastasis of patients, and could be used as an indicator of poor prognosis of NSCLC. However, the role of HNRNPC in regulating gene expression through m6A methylation modification in the occurance and progression of NSCLC remains largely unexplored. To investigate the target genes bound by HNRNPC, samples from A549 cells were harvested by RIP lysis buffer, and then the lysates were immunoprecipitated by 5μg anti-HNRNPC antibody. finally, the potential target genes were identified by RIP-seq.
2023-12-05 | GSE249094 | GEO
Project description:The m6A reader HNRNPC promotes non-small cell lung cancer progression by enhancing E2F2 mRNA stability
| PRJNA1047148 | ENA
Project description:Myelodysplastic Syndromes (MDS) result from expansion of defective hematopoietic stem/progenitor clones. There is an urgent need to develop targeted therapies capable of eliminating the defective MDS clones. We identified that IRAK1, an immune modulating kinase, is overexpressed and hyperactivated in MDS. MDS-propagating clones treated with a small-molecule IRAK1 inhibitor (IRAK1/4-Inh) exhibited impaired expansion and increased apoptosis, which coincided with TRAF6/NF-M-NM-:B inhibition. Suppression of IRAK1, either by RNAi or with IRAK1/4-Inh, is selectively detrimental to MDS clones as normal CD34+ cells are preserved. Based on conclusions derived from an integrative gene expression analysis, we combined IRAK1 and BCL2 inhibitors and found that co-treatment collaboratively and selectively eliminated MDS clones. In summary, these findings implicate IRAK1 as a drugable target in MDS. MDSL cells were transduced with lentivirus encoding shRNA targeting human IRAK1 and a negative control (pLKO) for 2.5 days. GFP positive cells were sorted for RNA extraction, labeling, and hybridization. A total of four samples were included, and two groups are assigned. Two replicates are for each group. Comparison comprises mRNA expression profile of TRAF6 knockdown (shT6) v.s. control vector (pLKO). Additionally, MDSL cells were treated with either DMSO or IRAK inhibitor for 24hrs. Cells were subjected to RNA extraction, labeling, and hybridization. A total of four samples were included, and two groups are assigned.
2013-04-25 | E-GEOD-46346 | biostudies-arrayexpress
Project description:Myelodysplastic Syndromes (MDS) result from expansion of defective hematopoietic stem/progenitor clones. There is an urgent need to develop targeted therapies capable of eliminating the defective MDS clones. We identified that IRAK1, an immune modulating kinase, is overexpressed and hyperactivated in MDS. MDS-propagating clones treated with a small-molecule IRAK1 inhibitor (IRAK1/4-Inh) exhibited impaired expansion and increased apoptosis, which coincided with TRAF6/NF-κB inhibition. Suppression of IRAK1, either by RNAi or with IRAK1/4-Inh, is selectively detrimental to MDS clones as normal CD34+ cells are preserved. Based on conclusions derived from an integrative gene expression analysis, we combined IRAK1 and BCL2 inhibitors and found that co-treatment collaboratively and selectively eliminated MDS clones. In summary, these findings implicate IRAK1 as a drugable target in MDS.
2013-04-25 | GSE46346 | GEO
Project description:The purpose of this experiment was to compare differences in Alu-exon inclusion in cells depleted of hnRNPC, Upf1, or both.
2016-04-01 | E-MTAB-4008 | biostudies-arrayexpress
Project description:HNRNPC plays an important role in HCC metastasis, HNRNPC knockdown by specific shRNA (HNRNPC-shRNA) significantly inhibited the migration and invasion of MHCC97H cells, while HNRNPC overexpression exerted the opposite effect. To elucidate the mechanisms by which HNRNPC facilitated HCC metastasis, we performed microarray analysis to compare the transcription profiling between the MHCC97H-shcontrol and MHCC97H-shHNRNPC cells.
2022-07-27 | GSE180789 | GEO
Project description:Interleukin-1 receptor associated kinase 1 (IRAK1) is an important component of the IL-1R and TLR signaling pathways, which influence Th cell differentiation. Here, we show that IRAK1 promotes Th17 development by mediating IL-1β induced upregulation of IL-23R and subsequent STAT3 phosphorylation, thus enabling sustained IL-17 production. Moreover, we show that IRAK1 signaling fosters Th1 differentiation by mediating T-bet induction and counteracts Treg generation. Cotransfer experiments revealed that Irak1-deficient CD4+ T cells have a cell-intrinsic defect in generating Th1 and Th17 cells under inflammatory conditions in spleen, mesenteric lymph nodes and colon tissue. Furthermore, IRAK1 expression in T cells was shown to be essential for T cell accumulation in the inflamed intestine and mLNs. Transcriptome analysis ex vivo revealed that IRAK1 promotes T cell activation and induction of gut-homing molecules in a cell-intrinsic manner. Accordingly, Irak1-deficient T cells failed to upregulate surface expression of α4β7 integrin after transfer into Rag1-/- mice and their ability to induce colitis was greatly impaired. Lack of IRAK1 in recipient mice provided additional protection from colitis. Therefore, IRAK1 plays an important role in intestinal inflammation by mediating T cell activation, differentiation and their accumulation in the gut. Thus, IRAK1 is a promising novel target for therapy of inflammatory bowel diseases.
2015-11-13 | GSE73875 | GEO
Project description:Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis, however its effects on cancer progression remain poorly understood. To address this, we used ribosome profiling to compare genome-wide translation efficiencies of poorly and highly metastatic breast cancer cells and patient-derived xenografts. We developed novel regression-based methods to analyze ribosome profiling and alternative polyadenylation data, and identified HNRNPC as a translational controller of a specific mRNA regulon. Mechanistically, HNRNPC, in concert with PABPC4, binds near to poly(A) signals, thereby governing the alternative polyadenylation of a set of mRNAs. We found that HNRNPC and PABPC4 are downregulated in highly metastatic cells, which causes HNRNPC-bound mRNAs to undergo 3’ UTR lengthening and subsequently, translational repression. We showed that modulating HNRNPC expression impacts the metastatic capacity of breast cancer cells in xenograft mouse models. We also found that a small molecule, previously shown to induce a distal-to-proximal poly(A) site switching, counteracts the HNRNPC-PABPC4 driven deregulation of alternative polyadenylation and decreases the metastatic lung colonization by breast cancer cells in vivo.
2023-02-20 | GSE186638 | GEO