Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia

ABSTRACT: RNA homeostasis is critical for cancer progression and therapy resistance. N6-methyladenosine (m6A), the most abundant epitranscriptomic modification in eukaryotic mRNA, has recently been found to be critical for various aspects of RNA biology, such as transcript stability, translation, and splicing. Our study showcases extensive m6A changes in T-cell acute lymphoblastic leukemia, affecting oncogenic MYC targets and cholesterol biosynthesis. We also demonstrate that leukemia cells strongly depend on the m6A reader HNRNPC, which we found to be a key regulator of these MYC targets and cholesterol biosynthesis. Consequently, HNRNPC silencing profoundly impaired these m6A-regulated pathways, resulting in significantly reduced leukemia growth. Corroborating results were collected by inhibiting the m6A demethylase FTO, which was demonstrated to be therapeutically relevant in preclinical disease models, while also synergizing with chemotherapeutics. Collectively, we reveal a novel role of m6A in coordinating the crosstalk between oncogenic expression and metabolism and provide therapeutic avenues against T-cell leukemia.

ORGANISM(S): Homo sapiens

PROVIDER: GSE272143 | GEO | 2025/08/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia- ONT DRS study

Project description:RNA homeostasis is dysregulated in cancer and impacts disease progression and therapy resistance. N6-methyladenosine (m6A), the most abundant epitranscriptomic modification in eukaryotic mRNA, plays a pivotal role in RNA biology, affecting transcript stability, translation, and splicing. Our study uncovers the extensive m6A changes in T-cell acute lymphoblastic leukemia (T-ALL) patient samples for the first time. It reveals m6A’s regulatory role in the oncogenic MYC and cholesterol biosynthesis pathways. In addition, we discovered that T-ALL is highly dependent on the m6A reader heterogeneous nuclear ribonucleoprotein C (HNRNPC). HNRNPC is transcriptionally controlled by MYC and is an essential regulator of m6A-modified transcripts. Consequently, transcriptional silencing of HNRNPC profoundly impairs oncogenic pathways and critically diminishes leukemia cell growth. Additionally, the levels of the m6A demethylase fat mass and obesity-associated (FTO) are significantly elevated in T-ALL cells compared to normal cells, and to other types of leukemia. Targeting FTO shows therapeutic potential in preclinical disease models and synergizes with clinically relevant therapeutics. Our findings underscore the integral role of RNA methylation in orchestrating cancer cell oncogene expression and metabolism, and highlight promising novel therapeutic avenues for the treatment of T-cell leukemia.

2025-08-06 | GSE289378 | GEO

The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway

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

HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia

Project description:HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia

| PRJNA1135200 | ENA

The m6A reader HNRNPC promotes non-small cell lung cancer progression by enhancing E2F2 mRNA stability

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

hNRNPC iCLIP

Project description:hNRNPC iCLIP

| PRJEB2253 | ENA

HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia- ONT DRS study

Project description:HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia- ONT DRS study

| PRJNA1222816 | ENA

Transcriptome profiling of cells depleted of hnRNPC, Upf1, or co-depleted of hnRNPC and Upf1.

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

Differentially expressed genes in HNRNPC knockdown MHCC97H cells

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

The aberrant inclusion of BOLA3 exon 3 promoted by HNRNPC acts as an oncogenic driver in esophageal squamous cell carcinoma [shHNRNPC RNA-seq]

Project description:Aberrant RNA splicing events produce transcripts to facilitate ESCC progression, yet how this splicing process is abnomally regulated remains elusive. Here, we unveil a alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC.The long isoform of BOLA3 (-L) with exon3 is highly expressed in ESCC and associated with poor prognosis. Functional assays demonstrate the pro-tumorigenic function of BOLA3-L in ESCC cells. HNRNPC binds to BOLA3-L pre-mRNA and promotes exon3 inclusion forming BOLA3-L. HNRNPC knockdown suppresses the tumorigenesis of ESCC cells, phenocopying BOLA3-L knockdown, which is significantly rescued by BOLA3-L overexpression. High expression of HNRNPC is correlated with the exon-3 inclusion of BOLA3 in ESCC and associated with poor prognosis. BOLA3-L maintains mitochondrial structural and functional stability, exerting pro-oncogenic effects through the WNT/β-catenin pathway. E2F7 acts as a key transcription factor to regulate the transcriptional upregulation of HNRNPC and promotes the inclusion of BOLA3 exon3.Taken together, our findings provide insights into how alternative splicing contributes to ESCC progression, by investgating a HNRNPC-BOLA3 splicing axis.

2024-01-01 | GSE235536 | GEO

The aberrant inclusion of BOLA3 exon 3 promoted by HNRNPC acts as an oncogenic driver in esophageal squamous cell carcinoma [11pairs RNA-seq]

2024-01-01 | GSE235537 | GEO