SREBF1 expression is associated with lipid metabolism-related signatures, and transient SREBF1 silencing is accompanied by increased apoptosis in pancreatic cancer cells.

Authors

Jiayi Wu, Danlei Ni, Kequn Xu

Published in

Molecular biology reports. Volume 53. Issue 1. Oct 12, 2026. Epub Oct 12, 2026.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by extensive metabolic adaptation. Sterol regulatory element-binding transcription factor 1 (SREBF1) encodes sterol regulatory element-binding protein 1 (SREBP1), a transcriptional regulator of lipogenic genes. This study investigated the association between SREBF1 expression and lipid metabolism-related transcriptional features in PDAC and assessed cellular responses to transient SREBF1 silencing.
SREBF1 expression was evaluated using RNA-sequencing data from TCGA-PAAD and GTEx and paired microarray data from GSE62452 and GSE183795. The analysis included 179 TCGA-PAAD tumors and 171 TCGA/GTEx non-tumor pancreatic samples, together with 61 matched tumor-adjacent pairs from GSE62452 and 102 matched pairs from GSE183795. TCGA-PAAD tumors were stratified at the median SREBF1 expression level for differential-expression analysis, GSEA, and GSVA. SREBF1 expression was higher in the TCGA/GTEx tumor-versus-normal comparison (P < 0.0001), with concordant increases in GSE62452 (P < 0.05) and GSE183795 (P < 0.01). SREBF1-high tumors exhibited lipid metabolism-related transcriptional features, including higher fatty-acid-metabolism and cholesterol-homeostasis pathway scores. In BxPC-3 and SW1990 cells, transient SREBF1 silencing with one selected siRNA was accompanied by decreased precursor SREBP1 (~ 122 kDa) and FASN protein levels, qualitatively reduced clonogenic outgrowth, and an increased Annexin V-positive apoptotic fraction.
SREBF1 expression is associated with lipid metabolism-related transcriptional features in PDAC. Transient SREBF1 silencing was accompanied by reduced FASN protein levels, qualitatively reduced clonogenic outgrowth, and increased apoptosis. These findings identify SREBP1-associated lipid metabolism as a candidate vulnerability that requires further validation but do not establish a direct SREBP1-FASN-cell-survival mechanism or therapeutic efficacy.

PMID:
42862406
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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