Expression of oxysterol pathway genes in oestrogen‐positive breast carcinomas

Kloudová, Alžběta; Brynychová, Veronika; Václavíková, Radka; Vrána, David; Gatěk, Jiří; Mrhalová, Marcela; Kodet, Roman; Souček, Pavel

doi:10.1111/cen.13337

Cited by 4 publications

(3 citation statements)

References 41 publications

(75 reference statements)

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“…Recent data have shown that major cholesterol metabolites, such as 27-hydroxycholesterol and 6-oxocholestan-3beta,5alpha-diol, display tumor-promoter properties 37 , 38 . Therefore, we further analyzed the expression of a curated list of 63 oxysterol pathway genes in mus musculus (Supplementary Data 5 ) known to be involved in the main oxysterol pathway, oxysterol metabolism, oxysterol pathway genes regulation and oxysterol transport 39 . We observed 47 (out of 63) dysregulated oxysterol pathway genes in dietary cholesterol-associated NASH-livers compared to non-cholesterol-associated steatosis-livers, as well as 33 dysregulated oxysterol pathway genes in cholesterol-associated NASH-HCCs compared to their adjacent non-tumor livers (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling

et al. 2018

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The underlining mechanisms of dietary cholesterol and nonalcoholic steatohepatitis (NASH) in contributing to hepatocellular carcinoma (HCC) remain undefined. Here we demonstrated that high-fat-non-cholesterol-fed mice developed simple steatosis, whilst high-fat-high-cholesterol-fed mice developed NASH. Moreover, dietary cholesterol induced larger and more numerous NASH-HCCs than non-cholesterol-induced steatosis-HCCs in diethylnitrosamine-treated mice. NASH-HCCs displayed significantly more aberrant gene expression-enriched signaling pathways and more non-synonymous somatic mutations than steatosis-HCCs (335 ± 84/sample vs 43 ± 13/sample). Integrated genetic and expressional alterations in NASH-HCCs affected distinct genes pertinent to five pathways: calcium, insulin, cell adhesion, axon guidance and metabolism. Some of the novel aberrant gene expression, mutations and core oncogenic pathways identified in cholesterol-associated NASH-HCCs in mice were confirmed in human NASH-HCCs, which included metabolism-related genes (ALDH18A1, CAD, CHKA, POLD4, PSPH and SQLE) and recurrently mutated genes (RYR1, MTOR, SDK1, CACNA1H and RYR2). These findings add insights into the link of cholesterol to NASH and NASH-HCC and provide potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling

et al. 2018

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“…Overall survival (OS) was calculated as the time from surgery to death or the last follow‐up date. The logistics of sample collection, storage, and processing have been described elsewhere [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we have therefore combined our existing somatic variation data from targeted DNA sequencing (DNA‐seq) of a panel of 113 oxysterol‐related genes (Table S1 , [ 15 ]) with respective mRNA expression data obtained by mRNA sequencing (mRNA‐seq) and with the complete miRNA transcriptome data obtained by microarrays, from the same BC patients. The genes and their roles in oxysterol signaling are summarized in our previous publications [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Integrative analysis of mRNA and miRNA expression profiles and somatic variants in oxysterol signaling in early‐stage luminal breast cancer

et al. 2023

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Oxysterols, oxidized derivatives of cholesterol, act in breast cancer (BC) as selective estrogen‐receptor modulators and affect cholesterol homeostasis, drug transport, nuclear and cell receptors, and other signaling proteins. Using data from three highly overlapping sets of patients (N=162 in total) with early‐stage estrogen‐receptor‐positive luminal BC—high‐coverage targeted DNA sequencing (113 genes), mRNA sequencing, and full micro‐RNA (miRNA) transcriptome microarrays—we describe complex oxysterol‐related interaction (correlation) networks, with validation in public datasets (n=538) and 11 databases. The ESR1‐CH25H‐INSIG1‐ABCA9 axis was the most prominent, interconnected through miR‐125b‐5p, miR‐99a‐5p, miR‐100‐5p, miR‐143‐3p, miR‐199b‐5p, miR‐376a‐3p and miR‐376c‐3p. Mutations in SC5D, CYP46A1, and its functionally linked gene set were associated with multiple differentially expressed oxysterol‐related genes. STARD5 was upregulated in patients with positive lymph‐node status. High expression of hsa‐miR‐19b‐3p was weakly associated with poor survival. This is the first study of oxysterol‐related genes in BC that combines DNA, mRNA and miRNA multi‐omics with detailed clinical data. Future studies should provide links between intra‐tumoral oxysterol signaling depicted here, circulating oxysterols levels, and therapy outcomes, enabling eventual clinical exploitation of present findings.

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Germline and somatic genetic variability of oxysterol-related genes in breast cancer patients with early disease of the luminal subtype

et al. 2022

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Expression of oxysterol pathway genes in oestrogen‐positive breast carcinomas

Cited by 4 publications

References 41 publications

Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling

Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling

Integrative analysis of mRNA and miRNA expression profiles and somatic variants in oxysterol signaling in early‐stage luminal breast cancer

Germline and somatic genetic variability of oxysterol-related genes in breast cancer patients with early disease of the luminal subtype

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