Explore the vast range of titles available.

Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, APOC1 gene is in linkage disequilibrium with APOE gene on chromosome 19, a proximity that spurred its investigation. Apolipoprotein C1 associates with triglyceride-rich lipoproteins and HDL and exchanges between lipoprotein classes. These interactions occur via amphipathic helix motifs, as demonstrated by biophysical studies on the wild-type polypeptide and representative mutants. Apolipoprotein C1 acts on lipoprotein receptors by inhibiting binding mediated by apolipoprotein E, and modulating the activities of several enzymes. Thus, apoC1 downregulates lipoprotein lipase, hepatic lipase, phospholipase A2, cholesterylester transfer protein, and activates lecithin-cholesterol acyl transferase. By controlling the plasma levels of lipids, apoC1 relates directly to cardiovascular physiology, but its activity extends beyond, to inflammation and immunity, sepsis, diabetes, cancer, viral infectivity, and—not last—to cognition. Such correlations were established based on studies using transgenic mice, associated in the recent years with GWAS, transcriptomic and proteomic analyses. The presence of a duplicate gene, pseudogene APOC1P, stimulated evolutionary studies and more recently, the regulatory properties of the corresponding non-coding RNA are steadily emerging. Nonetheless, this prototypical apolipoprotein is still underexplored and deserves further research for understanding its physiology and exploiting its therapeutic potential.

Identifying high-efficiency prognostic markers for colorectal cancer (CRC) is necessary for clinical practice. Increasing evidence demonstrates that apolipoprotein C1 (APOC1) promotes carcinogenesis in some human cancers. However, the expression status and biological function of APOC1 in CRC remain unclear. We detected the association between APOC1 expression and clinicopathological features in 140 CRC patients by immunohistochemistry. Small interfering RNA (siRNA) technology was used to downregulate APOC1 expression in CRC cells. Cell proliferation was estimated by CCK8 and clonogenic assays. The cell cycle and apoptosis were analyzed by flow cytometry. Cell migration and invasion were examined by a transwell assay. Gene set enrichment analysis (GSEA) and protein expression of signaling pathways were used to suggest the possible APOC1-associated pathways in CRC. APOC1 was highly expressed in CRC tissues. High immunohistochemistry (IHC) expression of APOC1 was correlated with the N stage, M stage and TNM stage. High IHC APOC1 expression in CRC tissues was associated with poor prognosis. Univariate and multivariate Cox regression analyses showed that APOC1 was an independent risk factor for OS. Cell proliferation of CRC cell lines was inhibited by the downregulation of APOC1. Moreover, si-APOC1 transfection induced cell cycle arrest but low apoptosis increases by regulating the expression of related proteins. Cell migration and invasion were also inhibited by the downregulation of APOC1. The Cancer Genome Atlas Colorectal Adenocarcinoma (TCGA COAD-READ) dataset analyzed by GSEA showed that APOC1 might be involved in the mitogen-activated protein kinase (MAPK) signaling pathway, which was further preliminarily confirmed by Western blotting. APOC1 was overexpressed in CRC tissues, and a high level of APOC1 contributed to a poor prognosis. APOC1 expression influenced the cell proliferation ability and motility capacity of CRC via the MAPK pathway. APOC1 could act as a novel prognostic biomarker in CRC.

Glioblastoma (GBM), a malignant brain tumor, is a world-wide health problem because of its poor prognosis and high rates of recurrence and mortality. Apolipoprotein C1 (APOC1) is the smallest of apolipoproteins, implicated in many diseases. Recent studies have shown that APOC1 promotes tumorigenesis and development of several types of cancer. In this study we investigated the role of APOC1 in GBM tumorigenesis. Using in silico assays we showed that APOC1 was highly expressed in GBM tissues and its expression was closely related to GBM progression. We showed that APOC1 protein expression was markedly increased in four GBM cell lines (U251, U138, A172 and U87) compared to the normal brain glia cell lines (HEB, HA1800). In U251 cells, overexpression of APOC1 promoted cell proliferation, migration, invasion and colony information, which was reversed by APOC1 knockdown. APOC1 knockdown also markedly inhibited the growth of GBM xenografts in the ventricle of nude mice. We further demonstrated that APOC1 reduced ferroptosis by inhibiting KEAP1, promoting nuclear translocation of NRF2 and increasing expression of HO-1 and NQO1 in GBM cells. APOC1 also induced ferroptosis resistance by increasing cystathionine beta-synthase (CBS) expression, which promoted trans-sulfuration and increased GSH synthesis, ultimately leading to an increase in glutathione peroxidase-4 (GPX4). Thus, APOC1 plays a key role in GBM tumorigenesis, conferring resistance to ferroptosis, and may be a promising therapeutic target for GBM.

Abstract Context Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important to deeply characterize the human nutritional responses. Objective Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers. Methods We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) 10 healthy, young, male individuals in response to 2 days of acute caloric restriction followed by refeeding; ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at 4 time points (0, 30, 60, 120 minutes); and iii) 200 random individuals from the Generation Scotland study. We compared the proteomic changes detected with metabolome data and endocrine parameters. Results Both caloric restriction and the glucose challenge substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identified nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes. Conclusion Our study identifies APOC1 as a dominant nutritional responder in humans and highlights the interdependency of acute nutritional response proteins and the endocrine system.

Background Recent studies have demonstrated that APOC1 is associated with cancer progression, exerting cancer-promoting and immune infiltration-promoting effects. Nevertheless, there is currently no report on the presence of APOC1 in ovarian cancer (OV). Method In this study, we conducted data analysis using the GEO and TCGA databases. We conducted a thorough bioinformatics analysis to investigate the function of APOC1 in OV, utilizing various platforms including cBioPortal, STRING, GeneMANIA, LinkedOmics, GSCALite, TIMER, and CellMarker. Additionally, we performed immunohistochemical staining on tissue microarrays and conducted in vitro cellular assays to validate our findings. Result Our findings reveal that APOC1 expression is significantly upregulated in OV compared to normal tissues. Importantly, patients with high APOC1 levels show a significantly poorer prognosis. Furthermore, our study demonstrated that APOC1 exerted a crucial function in promoting the capacity of ovarian cancer cells to proliferate, migrate, and invade. Additionally, we have identified that genes co-expressed with APOC1 are primarily associated with adaptive immune responses. Notably, the levels of APOC1 in OV exhibit a correlation with the presence of M2 Tumor-associated Macrophages (TAMs). Conclusion APOC1 emerges as a promising prognostic biomarker for OV and exhibits a significant association with M2 TAMs in OV.

Previous reports showed that was associated with several cancers but the function of in cervical cancer was unknown. This study aimed to investigate the clinical effect and function of in cervical cancer. In this study, the relative expression of in cervical cancer was detected by RT-qPCR. In order to determine the cell proliferation and migration and invading ability and apoptosis more accurately, we used CCK8 assay, Edu assay, wound healing assay, migration and invasion assay, flow cytometry assay, co-immunoprecipitation, proteomics and Western blot by silencing and overexpressing , respectively. The role of on tumor progression was explored in vitro and vivo. The relative expression of in cervical cancer tissues was up-regulated (P<0.05). In cervical cancer cell lines, silencing of restrained cell progression and EMT, while over-expression of accelerated cell progression and EMT in vivo and vitro (P<0.05). acts as an oncogene in cervical cancers and knockdown of inhibited cervical cancer cells growth in vitro and in vivo. There is a close relationship between the relative expression of and clinical outcome in cervical cancer patients.

[This corrects the article DOI: 10.3389/fcvm.2024.1381520.].

Renal cell carcinoma (RCC) is one of the most prevalent categories of cancer worldwide, accounting for approximately 2% of cancer diagnoses and cancer deaths worldwide. various immunotherapeutic strategies have emerged as key approaches to managing advanced RCC. Bioinformatics methodologies were employed to analyze the TCGA-KIRC RNA sequencing dataset, GSE105261, GSE168845, and single-cell dataset GSE121636. Various techniques, including PCR, Western blotting, migration assays, scratch wound assays, flow cytometry, and immunofluorescence staining, were utilized to elucidate the functional characteristics of the tumor. In this study, we obtained transcriptome RNA sequencing data from the Cancer Genome Atlas (TCGA) database. Using the ESTIMATE algorithm, 249 immune-related genes were identified. Additionally, single-cell RNA sequencing data were integrated to determine the immune-related genes that affect the prognosis of clear cell renal cell carcinoma (ccRCC). Eventually, a total of 42 immune-related genes (IMDGs) were identified. Subsequently, in vitro experiments confirmed that APOC1 is highly expressed in ccRCC and significantly affects the migration and proliferation of ccRCC cells. Furthermore, our findings indicate that APOC1 plays a critical role in modulating cholesterol transport within macrophages and significantly contributes to the polarization of macrophages toward the M2 phenotype.

The ε4 allele of the apolipoprotein E (APOE) gene strongly increases Alzheimer’s disease (AD) risk, though its molecular mechanisms remain unclear. AD-associated genetic signals also extend to neighboring genes TOMM40 and APOC1, suggesting a complex cis-regulatory landscape. To investigate chromatin architecture and its impact on gene regulation across this region, we performed chromosome conformation capture in human cell lines and postmortem brain tissues, consistently identifying TOMM40–APOE and APOE–APOC1 interactions. We further developed a digital PCR assay to quantify APOE–APOC1 interaction strength and measured APOC1 mRNA via RT-qPCR. Enhanced chromatin interaction correlated with elevated APOC1 transcription in AD specimens. Genotypic analysis showed that ε3/ε4 carriers had strong chromatin interaction and transcriptional activation, whereas ε4/ε4 homozygotes exhibited minimal chromatin remodeling despite similar APOC1 expression, suggesting a decoupling of chromatin architecture and transcriptional output. These findings underscore the interplay of AD status, APOE genotype, and locus-specific chromatin dynamics in disease susceptibility. Integration of 3D genome topology with transcriptomic profiling offers a framework to study APOE-related disorders and supports broader application across neurodegenerative loci for genotype-guided therapy development.

Gemcitabine is used to treat pancreatic cancer (PC), but is not curative. We sought to determine whether gemcitabine + a BET bromodomain inhibitor was superior to gemcitabine, and identify proteins that may contribute to the efficacy of this combination. This study was based on observations that cell cycle dysregulation and DNA damage augment the efficacy of gemcitabine. BET inhibitors arrest cells in G1 and allow increases in DNA damage, likely due to inhibition of expression of DNA repair proteins Ku80 and RAD51. BET inhibitors (JQ1 or I-BET762) + gemcitabine were synergistic in vitro, in Panc1, MiaPaCa2 and Su86 PC cell lines. JQ1 + gemcitabine was more effective in vivo than either drug alone in patient-derived xenograft models (P < 0.01). Increases in the apoptosis marker cleaved caspase 3 and DNA damage marker γH2AX paralleled antitumor efficacy. Notably, RNA-seq data showed that JQ1 + gemcitabine selectively inhibited HMGCS2 and APOC1 ~6-fold, compared to controls. These proteins contribute to cholesterol biosynthesis and lipid metabolism, and their overexpression supports tumor cell proliferation. IPA data indicated that JQ1 + gemcitabine selectively inhibited the LXR/RXR activation pathway, suggesting the hypothesis that this inhibition may contribute to the observed in vivo efficacy of JQ1 + gemcitabine.