Search results for: FBXL3
#39357875 2024/10/02 To Up
Regular exercise suppresses steatosis-associated liver cancer development by degrading E2F1 and c-Myc via circadian gene upregulation.
Regular exercise is believed to suppress cancer progression. However, the precise molecular mechanisms by which exercise prevents cancer development remain unclear. In this study, using a steatosis-associated liver cancer mouse model, we found that regular exercise at a speed of 18 m/min for 20 min daily suppressed liver cancer development. To explore the underlying mechanisms, we examined the gene expression profiles in the livers of the exercise and non-exercise groups. The expressions of circadian genes, such as Per1 and Cry2, were upregulated in the exercise group. As circadian rhythm disruption is known to cause various diseases, including cancer, improving circadian rhythm through exercise could contribute to cancer prevention. We further found that the expression of a series of E2F1 and c-Myc target genes that directly affect the proliferation of cancer cells was downregulated in the exercise group. However, the expression of E2F1 and c-Myc was transcriptionally unchanged but degraded at the post-translational level by exercise. Cry2, which is regulated by the Skp1-Cul1-FBXL3 (SCF) ubiquitin ligase complex by binding to FBXL3, can form a complex with E2F1 and c-Myc, which we think is the mechanism to degrade them. Our study revealed a previously unknown mechanism by which exercise prevents cancer development.Vu Thuong Huyen, Kanae Echizen, Ryota Yamagishi, Miho Kumagai, Yoshiki Nonaka, Takahiro Kodama, Tatsuya Ando, Megumu Yano, Naoki Takada, Masaki Takasugi, Fumitaka Kamachi, Naoko Ohtani
1064 related Products with: Regular exercise suppresses steatosis-associated liver cancer development by degrading E2F1 and c-Myc via circadian gene upregulation.
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#39281811 2024/08/30 To Up
The genetic cause of neurodevelopmental disorders in 30 consanguineous families.
This study aims to clinically and genetically assess 30 unrelated consanguineous Pakistani families from various ethnic backgrounds, all exhibiting features of neurodevelopmental disorders (NDDs).Sohail Aziz Paracha, Shoaib Nawaz, Muhammad Tahir Sarwar, Asmat Shaheen, Gohar Zaman, Jawad Ahmed, Fahim Shah, Sundus Khwaja, Abid Jan, Nida Khan, Mohammad Azhar Kamal, Qamre Alam, Safdar Abbas, Saman Farman, Ahmed Waqas, Afnan Alkathiri, Abdullah Hamadi, Federico Santoni, Naseeb Ullah, Bisma Khalid, Stylianos E Antonarakis, Khalid A Fakhro, Muhammad Umair, Muhammad Ansar
1367 related Products with: The genetic cause of neurodevelopmental disorders in 30 consanguineous families.
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#39193850 // To Up
A majority of circadian clock genes are expressed in estrogen receptor and progesterone receptor status-dependent manner in breast cancer.
Circadian clocks, biochemical oscillators that are regulated by environmental time cues including the day/night cycle, have a central function in the majority of biological processes. The disruption of the circadian clock can alter breast biology negatively and may promote the development of breast tumors. The expression status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) were used to classify breast cancer into different molecular subtypes such as triple-negative breast cancer (TNBC). Receptor status-dependent expression of circadian clock genes have been previously studied in breast cancer using relatively small sample sizes in a particular population. Here, using TCGA-BRCA data (=1119), we found that the expressions of and were higher in ER+ breast cancer cells compared with those of ER- status. Similarly, we showed that transcript levels of and were higher in PR+ breast cancer cells than in PR- breast cancer cells. We report that the expressions of and were lower, and the expression of was higher, in HER2+ breast cancer cells compared with HER2- breast cancer cells. Moreover, we studied these receptor status-dependent changes in the expressions of circadian clock genes also based on the race and age of breast cancer patients. Lastly, we found that the expressions of and were higher in non-TNBC than in TNBC, which has the worst prognosis among subtypes. We note that our findings are not always parallel to the observations reported in previous studies with smaller sample sizes performed in different populations and organisms. Our study suggests that receptor status in breast cancer (thus, subtype of breast cancer) might be more important than previously shown in terms of its influence on the expression of circadian clock genes and on the disruption of the circadian clock, and that ER or PR might be important regulators of breast cancer chronobiology that should be taken into account in personalized chronotherapies.Caglar Berkel, Ercan Cacan
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#39051074 // To Up
[Tumor-associated fibroblasts promotes proliferation and migration of prostate cancer cells by suppressing FBXL3 upregulating hsa-miR-18b-5p].
To explore the mechanism of tumor-associated fibroblasts (CAFs) for regulating proliferation and migration of prostate cancer (PCa) cells.J Luo, H Tao, Z Wen, L Chen, H Hu, H Guan
1994 related Products with: [Tumor-associated fibroblasts promotes proliferation and migration of prostate cancer cells by suppressing FBXL3 upregulating hsa-miR-18b-5p].
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#38788553 2024/05/10 To Up
Sex-specific associations between circadian-related genes and depression in UK Biobank participants highlight links to glucose metabolism, inflammation and neuroplasticity pathways.
Depressive disorders have increased in global prevalence, making improved management of these disorders a public health priority. Prior research has linked circadian clock genes to depression, either through direct interactions with mood-related pathways in the brain or by modulating the phase of circadian rhythms. Using machine learning and statistical techniques, we explored associations between 157,347 SNP variants from 51 circadian-related genes and depression scores from the patient health questionnaire 9 (PHQ-9) in 99,939 UK Biobank participants. Our results highlight multiple pathways linking the circadian system to mood, including metabolic, monoamine, immune, and stress-related pathways. Notably, genes regulating glucose metabolism and inflammation (GSK3B, LEP, RORA, and NOCT) were prominent factors in females, in addition to DELEC1 and USP46, two genes of unknown function. In contrast, FBXL3 and DRD4 emerged as significant risk factors for male depression. We also found epistatic interactions involving RORA, NFIL3, and ZBTB20 as either risk or protective factors for depression, underscoring the importance of transcription factors (ZBTB20, NFIL3) and hormone receptors (RORA) in depression etiology. Understanding the complex, sex-specific links between circadian genes and mood disorders will facilitate the development of therapeutic interventions and enhance the efficacy of multi-target treatments for depression.Mete Minbay, Ayub Khan, Ali R Ghasemi, Krista K Ingram, Ahmet A Ay
1559 related Products with: Sex-specific associations between circadian-related genes and depression in UK Biobank participants highlight links to glucose metabolism, inflammation and neuroplasticity pathways.
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#38781400 2024/05/23 To Up
Erratum for the Report "SCF controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins" by L. Busino .
1591 related Products with: Erratum for the Report "SCF controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins" by L. Busino .
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#38726735 2024/05/10 To Up
Whole-genome resequencing deciphers patterns of genetic diversity, phylogeny, and evolutionary dynamics in Kashmir cattle.
Kashmir cattle, which were kept by local pastoralists for centuries, are exceptionally resilient and adaptive to harsh environments. Despite its significance, the genomic characteristics of this cattle breed remain elusive. This study utilized whole genome sequences of Kashmir cattle (n = 20; newly sequenced) alongside published whole genomes of 32 distinct breeds and seven core cattle populations (n = 135). The analysis identified ~25.87 million biallelic single nucleotide polymorphisms in Kashmir cattle, predominantly in intergenic and intron regions. Population structure analyses revealed distinct clustering patterns of Kashmir cattle with proximity to the South Asian, African and Chinese indicine cattle populations. Genetic diversity analysis of Kashmir cattle demonstrated lower inbreeding and greater nucleotide diversity than analyzed global breeds. Homozygosity runs indicated less consanguineous mating in Kashmir cattle compared with European taurine breeds. Furthermore, six selection sweep detection methods were used within Kashmir cattle and other cattle populations to identify genes associated with vital traits, including immunity (BOLA-DQA5, BOLA-DQB, TNFAIP8L, FCRL4, AOAH, HIF1AN, FBXL3, MPEG1, CDC40, etc.), reproduction (GOLGA4, BRWD1, OSBP2, LEO1 ADCY5, etc.), growth (ADPRHL1, NRG2, TCF12, TMOD4, GBP4, IGF2, RSPO3, SCD, etc.), milk composition (MRPS30 and CSF1) and high-altitude adaptation (EDNRA, ITPR2, AGBL4 and SCG3). These findings provide essential genetic insights into the characteristics and establish the foundation for the scientific conservation and utilization of Kashmir cattle breed.Zulfiqar Ahmed, Weixuan Xiang, Fuwen Wang, Mohsin Nawaz, Zulfiqar Hussan Kuthu, Chuzhao Lei, Dequan Xu
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#38518666 2024/01/24 To Up
Effects of 28 h ahemeral light cycle on production performance, egg quality, blood parameters, and uterine characteristics of hens during the late laying period.
This study aimed to systematically determined the effect of 28 h ahemeral light cycle on production performance, egg quality, blood parameters, uterine morphological characteristics, and gene expression of hens during the late laying period. At 74 wk, 260 Hy-Line Brown layers were randomly divided into 2 groups of 130 birds each and in duplicates. Both a regular (16L:8D) and an ahemeral light cycle (16L:12D) were provided to the hens. The oviposition pattern in an ahemeral cycle shifted into darkness, with oviposition mostly occurring 3 to 5 h after light out. Production performance was unaffected by light cycle (P > 0.05). Nonetheless, compared to the normal group, the ahemeral group exhibited increased egg weight, eggshell weight, eggshell percentage, yolk percentage, eggshell thickness, and eggshell strength (P < 0.05). There were rhythmic changes in the uterine morphological structure in both cycles, however, the ahemeral group maintained a longer duration and had more uterine folds than the normal group. In the ahemeral cycle, the phases of the CLOCK and PER2 genes were phase-advanced for 3.96 h and 4.54 h compared to the normal cycle. The PHLPP1 gene, which controls clock resetting, exhibited a substantial oscillated rhythm in the ahemeral group (P < 0.05), while the expression of genes presenting biological rhythm, such as CRY2 and FBXL3, was rhythmically oscillated in normal cycle (P < 0.05). The ITPR2 gene, which regulates intracellular Ca transport, displayed a significant oscillated rhythm in ahemeral alone (P < 0.05), while the CA2 gene, which presents biomineralization, rhythmically oscillated in both cycles (P < 0.05). The ahemeral cycle caused 2.5 h phase delays in the CA2 gene compared to the normal cycle. In conclusion, the 28 h ahemeral light cycle preserved the high condition of the uterine folds and changed the uterine rhythms of CLOCK, PER2, ITPR2, and CA2 gene expression to improve ion transport and uterine biomineralization.Xuelu Liu, Lei Shi, Erying Hao, Xiangyu Chen, Ziwen Liu, Yifan Chen, Dehe Wang, Chenxuan Huang, Jiawei Ai, Min Wu, Yanyan Sun, Yunlei Li, Lijun Xu, Erdong Sun, Jilan Chen, Hui Chen
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#38093312 2023/12/13 To Up
Histone demethylase KDM4B accelerates the progression of glioblastoma via the epigenetic regulation of MYC stability.
Glioblastoma (GBM) is the most malignant and invasive human brain tumor. Histone demethylase 4B (KDM4B) is abnormally expressed in GBM, but the molecular mechanisms by which KDM4B affects the malignant tumor progression are not well defined.Zhongze Wang, Huarui Cai, Zekun Li, Wei Sun, Erhu Zhao, Hongjuan Cui
2334 related Products with: Histone demethylase KDM4B accelerates the progression of glioblastoma via the epigenetic regulation of MYC stability.
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#37951306 2023/11/10 To Up
Functional characterization of the CRY2 circadian clock component variant p.Ser420Phe revealed a new degradation pathway for CRY2.
Cryptochromes (CRYs) are essential components of the circadian clock, playing a pivotal role as transcriptional repressors. Despite their significance, the precise mechanisms underlying CRYs' involvement in the circadian clock remain incompletely understood. In this study, we identified a rare CRY2 variant, p.Ser420Phe, from the 1000 Genomes Project and Ensembl database that is located in the functionally important coiled-coil-like helix (CC-helix) region. Functional characterization of this variant at the cellular level revealed that p.Ser420Phe CRY2 had reduced repression activity on CLOCK:BMAL1-driven transcription due to its reduced affinity to the core clock protein PER2 and defective translocation into the nucleus. Intriguingly, the CRY2 variant exhibited an unexpected resistance to degradation via the canonical proteasomal pathway, primarily due to the loss of interactions with E3 ligases (FBXL3 and FBXL21), which suggests Ser-420 of CRY2 is required for the interaction with E3 ligases. Further studies revealed that wild-type and CRY2 variants are degraded by the lysosomal-mediated degradation pathway, a mechanism not previously associated with CRY2. Surprisingly, our complementation study with Cry1Cry2 double knockout mouse embryonic fibroblast cells indicated that the CRY2 variant caused a 7 h shorter circadian period length in contrast to the observed prolonged period length in CRY2 cell lines. In summary, this study reveals a hitherto unknown degradation pathway for CRY2, shedding new light on the regulation of circadian rhythm period length.Gizem Cagla Parlak, Ibrahim Baris, Seref Gul, Ibrahim Halil Kavakli
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