Personal communication between Dr. Feo and the RGD curators. He refers to the breast cancer paper by Shepel LA, etal., Genetics 1998 May;149(1):289-99 61081 and liver cancer paper by De Miglio MR, etal., Cancer Res 2002 Aug 1;62(15):445
Barclay SF, etal., Respir Physiol Neurobiol. 2016 Jan 15;221:59-63. doi: 10.1016/j.resp.2015.11.002. Epub 2015 Nov 10.
BACKGROUND AND OBJECTIVES: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare pediatric disease of unknown cause. Here, in response to a recent case report describing a ROHHAD patient who suffered from secondary narcolepsy confirmed by
an absence of hypocretin-1 in the cerebrospinal fluid, we consider whether the ROHHAD phenotype is owing to one or more mutations in genes specific to hypocretin protein signalling. METHODS: DNA samples from 16 ROHHAD patients were analyzed using a combination of next-generation and Sanger sequencing to identify exonic sequence variations in three genes: HCRT, HCRTR1, and HCRTR2. RESULTS: No rare or novel mutations were identified in the exons of HCRT, HCRTR1, or HCRTR2 genes in a set of 16 ROHHAD patients. CONCLUSIONS: ROHHAD is highly unlikely to be caused by mutations in the exons of the genes for hypocretin and its two receptors.
Chen Y, etal., Med Oncol. 2016 Jan;33(1):3. doi: 10.1007/s12032-015-0713-9. Epub 2015 Nov 25.
The objective of the study was to investigate the role of hcrcn81 gene in Wnt/beta-catenin signaling pathway related to human colorectal cancer. A total of 30 pairs of human colorectal cancer tissues with control normal tissues were analyzed by qRT-PCR. The prol
iferation, apoptosis, cell cycle, cell colony and metastasis of LS174T(-hcrcn81), HCT116(-hcrcn81), LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) cells were tested, of which hcrcn81 was knockdown in LS174T, HCT116 cells and hcrcn81 was overexpressed in LoVo, SMMC-7721 cells. Besides, the mRNA and protein levels of hcrcn81, beta-catenin, c-Myc, cyclinD1, GSK-3beta and survivin in colon cancer cell lines were evaluated by qRT-PCR and western blot. The mRNA levels of beta-catenin and Survivin were up-regulated in 76.7 % (23/30) and 63.3 % (19/30) of the tumor samples, respectively. hcrcn81 and GSK-3beta mRNA expression levels were down-regulated in 20/30 (66.7 %) and 21/30 (70.0 %) of the tumor samples as compared to the adjacent normal tissues, respectively. Furthermore, in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) cells, the mRNA and protein levels of beta-catenin, c-Myc, cyclinD1 and Survivin were up-regulated, whereas those of GSK-3 were down-regulated. In LS174T(-hcrcn81) and HCT116(-hcrcn81) cells, the mRNA levels of beta-catenin, c-Myc, cyclinD1 and Survivin were down-regulated, whereas GSK-3betamRNA was up-regulated. Cell proliferation in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) groups was significantly enhanced (P < 0.05). Proliferation index in both LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) groups was significantly higher than that in the control groups (P < 0.05). The number of colony in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) cells were significantly higher than that in the control groups (P < 0.05). In addition, the percentage of apoptotic cells in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) groups were significantly lower than that in the control groups (P < 0.01, P < 0.01). Finally, the number of migrating cells was significantly higher in LoVo(+hcrcn81) and SMMC-7721(+hcrcn81) groups than that in the control group (P < 0.05). hcrcn81 might promote carcinogenesis and progression through regulation of the Wnt/beta-catenin signaling pathway and plays an important role in the carcinogenesis of colorectal cancer.
Fan Z, etal., J Headache Pain. 2018 Jan 9;19(1):1. doi: 10.1186/s10194-017-0831-1.
BACKGROUND: Cluster headache (CH), a rare primary headache disorder, is currently thought to be a genetic susceptibility which play a role in CH susceptibility. A large numbers of genetic association studies have confirmed that the HCRTR2 (Hypocretin
Receptor 2) SNP rs2653349, and the ADH4 (Alcohol Dehydrogenase 4) SNP rs1126671 and rs1800759 polymorphisms are linked to CH. In addition, the CLOCK (Circadian Locomotor Output Cycles Kaput) gene is becoming a research hotspot for CH due to encoding a transcription factor that serves as a basic driving force for circadian rhythm in humans. The purpose of this study was to evaluate the association between CH and the HCRTR2, ADH4 and CLOCK genes in a Chinese CH case-control sample. METHODS: We genotyped polymorphisms of nine single nucleotide polymorphisms (SNPs) in the HCRTR2, ADH4 and CLOCK genes to perform an association study on a Chinese Han CH case-control sample (112 patients and 192 controls),using Sequenom MALDI-TOF mass spectrometry iPLEX platform. The frequencies and distributions of genotypes and haplotypes were statistically compared between the case and control groups to identify associations with CH. The effects of SNPs on CH were further investigated by multiple logistic regression. RESULTS: The frequency of the HCRTR2 SNP rs3800539 GA genotype was significantly higher in cases than in controls (48.2% vs.37.0%). The GA genotypes was associated with a higher CH risk (OR = 1.483, 95% CI: 0.564-3.387, p = 0.038), however, after Bonferroni correction, the association lost statistical significance. Haplotype analysis of the HCRTR2 SNPs showed that among eight haplotypes, only H1-GTGGGG was linked to a reduced CH risk (44.7% vs. 53.1%, OR = 0.689, 95% CI =0.491~0.966, p = 0.030). No significant association of ADH4, CLOCK SNPs with CH was statistically detected in the present study. CONCLUSIONS: Association between HCRTR2, ADH4,CLOCK gene polymorphisms and CH was not significant in the present study, however, haplotype analysis indicated H1-GTGGGG was linked to a reduced CH risk.
Chen F, etal., Sci Rep. 2015 Aug 25;5:13470. doi: 10.1038/srep13470.
Previous studies indicated a role of hepatocellular carcinoma-related protein-1(HCRP-1) in human cancers, however, its expression pattern in renal cell carcinoma (RCC) and the molecular mechanism of HCRP-1 on cancer progress
ion have not been characterized. In the present study, HCRP-1 expression was examined in a RCC tissue microarray. The negative expression of HCRP-1 was significantly correlated with tumor grade (P = 0.002), TNM stage (P = 0.001) and pT status (P = 0.003). Furthermore, we showed a strong correlation between negative HCRP-1 expression and worse overall and disease-specific survival (P = 0.0003 and P = 0.0012, respectively). Knockdown of HCRP-1 promoted cell migration and invasion in 786-O and OS-RC-2 cell lines. HCRP-1 depletion increased matrix metalloproteinase (MMP)-2 protein level, with increased extracellular signal-regulatedkinase (ERK) phosphorylation, which could be reversed by ERK siRNA or ERK inhibitor, PD98059. Further analysis showed that HCRP-1 knockdown induced epidermal growth factor receptor (EGFR) phosphorylation. Treatment with EGFR inhibitor or EGFR siRNA blocked HCRP-1-mediated up-regulation of EGFR, ERK phosphorylation and MMP-2 expression. In summary, our results showed that negative HCRP-1 expression is an independent prognostic factor for RCC patients and promotes migration and invasion by EGFR-ERK-mediated up-regulation of MMP-2. HCRP-1 may serve as a therapeutic target for RCC.
Zhao S and Sancar A, Photochem Photobiol. 1997 Nov;66(5):727-31.
Photolyase/blue-light photoreceptor family of proteins includes cyclobutane pyrimidine dimer photolyase, (6-4) photolyase and blue-light photoreceptors that were recently discovered in Arabidopsis thaliana, Sinapis alba and Chlamydomonas reinhardtii. Recently, we identified two human genes, hCRY1
and hCRY2, belonging to this family. The proteins encoded by these genes have no DNA repair activity and therefore were hypothesized to function in human blue-light response reactions. To identify downstream targets for these putative blue-light photoreceptors we searched for interacting proteins by the yeast two-hybrid method. We found that the tetratricopeptide repeat protein 1, Tpr1, and the protein serine/threonine phosphatase 5 (PP5) that contains the TPR motif specifically interacted with hCRY2. The effect of the hCRY2-PP5 interaction on the protein phosphatase activity was investigated. We found that hCRY2, but not the highly homologous (6-4) photolyase, inhibits the phosphatase activity of PP5. This inhibition may be on the pathway of blue-light signal transduction reaction in humans.
