PKMYT1 knockdown inhibits cholesterol biosynthesis and promotes the drug sensitivity of triple-negative breast cancer cells to atorvastatin DOI Creative Commons
Wei Gao, Xin Guo, Linlin Sun

и другие.

PeerJ, Год журнала: 2024, Номер 12, С. e17749 - e17749

Опубликована: Июль 12, 2024

Triple negative breast cancer (TNBC) as the most aggressive molecular subtype of is characterized by high cell proliferation and poor patient prognosis. Abnormal lipid metabolism contributes to malignant process cancers. Study observed significantly enhanced cholesterol biosynthesis in TNBC. However, mechanisms underlying abnormal increase TNBC are still unclear. Hence, we identified a member serine/threonine protein kinase family PKMYT1 key driver synthesis cells. Aberrantly high-expressed was indicative unfavorable prognostic outcomes. In addition, promoted sterol regulatory element-binding 2 (SREBP2)-mediated expression enzymes related through activating TNF/ TNF receptor-associated factor 1 (TRAF1)/AKT pathway. Notably, downregulation inhibited feedback upregulation statin-mediated biosynthesis, whereas knockdown drug sensitivity atorvastatin Overall, our study revealed novel function providing new target for targeting tumor metabolic reprogramming cancer.

Язык: Английский

Predicting survival and immune status of breast cancer patients based on prognostic features related to PANoptosis DOI Creative Commons
Jing Cui, Dapeng Wu, Da Lv

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 15, 2025

Breast cancer (BRCA) is a prevalent female malignancy. PANoptosis, integrating diverse cell death traits, pivotal in BRCA, thus necessitating deeper study. Data from Gene Expression Omnibus (GEO, GSE180286 and GSE20685) The Cancer Genome Atlas (TCGA) were analyzed. Weighted gene co-expression network analysis (WGCNA) identified PANoptosis-related genes BRCA patients TCGA. Further refinement of these module was conducted through univariate Cox regression, LASSO regression (glmnet package), stepwise multivariate to derive the final biomarkers. Based on biomarkers, risk model established, in-vitro experiments (wound healing assay, Transwell qRT-PCR) carried out validate accuracy MCPcounter package oncoPredict used assess immune infiltration sensitivity drugs patients, respectively. This study 8 biomarkers (ACY3, CD83, CXCL13, KLHDC7B, NR1H3, SMCO4, TRPM2, UPP1) established model. In-vitro revealed significant differences biomarker expression between cells control group, with TRPM2 knockdown inhibiting migration invasion. Enrichment showed metabolic pathways activated high-risk group. Additionally, lower enrichment fibroblasts Drug linked 13 RiskScore. Finally, single-cell six types (including stem cells, fibroblasts, T-cells, macrophages, B/Plasma endothelial cells) for found that macrophages had higher PANoptosis activity. current research introduces novel prognosis but also provides fresh perspective treatment strategies.

Язык: Английский

Процитировано

0
PKMYT1 knockdown inhibits cholesterol biosynthesis and promotes the drug sensitivity of triple-negative breast cancer cells to atorvastatin DOI Creative Commons
Wei Gao, Xin Guo, Linlin Sun

и другие.

PeerJ, Год журнала: 2024, Номер 12, С. e17749 - e17749

Опубликована: Июль 12, 2024

Triple negative breast cancer (TNBC) as the most aggressive molecular subtype of is characterized by high cell proliferation and poor patient prognosis. Abnormal lipid metabolism contributes to malignant process cancers. Study observed significantly enhanced cholesterol biosynthesis in TNBC. However, mechanisms underlying abnormal increase TNBC are still unclear. Hence, we identified a member serine/threonine protein kinase family PKMYT1 key driver synthesis cells. Aberrantly high-expressed was indicative unfavorable prognostic outcomes. In addition, promoted sterol regulatory element-binding 2 (SREBP2)-mediated expression enzymes related through activating TNF/ TNF receptor-associated factor 1 (TRAF1)/AKT pathway. Notably, downregulation inhibited feedback upregulation statin-mediated biosynthesis, whereas knockdown drug sensitivity atorvastatin Overall, our study revealed novel function providing new target for targeting tumor metabolic reprogramming cancer.

Язык: Английский

Процитировано

1