ZIC1 Is Downregulated through Promoter Hypermethylation, and Functions as a Tumor Suppressor Gene in Colorectal Cancer

The transcription factor, Zinc finger of the cerebellum (ZIC1), plays a crucial role in vertebrate development. Recently, ZIC1 has also been found to participate in the progression of human cancers, including medulloblastomas, endometrial cancers, and mesenchymal neoplasms. However, the function of ZIC1 in colon cancer progression has not been defined. In this study, we demonstrate ZIC1 to be silenced or significantly downregulated in colon cancer cell lines. These effects were reversed by demethylation treatment with 5-aza-2′-deoxycytidine (Aza). ZIC1 expression is also significantly downregulated in primary colorectal cancer tissues relative to adjacent non-tumor tissues (p = 0.0001). Furthermore, methylation of ZIC1 gene promoter is frequently detected in primary tumor tissues (85%, 34/40), but not in adjacent non-tumor tissues. Ectopic expression of ZIC1 suppresses cell proliferation and induces apoptosis, which is associated with MAPK and PI3K/Akt pathways, as well as the Bcl-xl/Bad/Caspase3 cascade. To identify target candidates of ZIC1, we employed cDNA microarray and found that 337 genes are downregulated and 95 genes upregulated by ectopic expression of ZIC1, which were verified by 10 selected gene expressions by qRT-PCR. Taken together, our results suggest that ZIC1 may potentially function as a tumor suppressor gene, which is downregulated through promoter hypermethylation in colorectal cancers

Chitosan extraction from lobster shells and its grafted with functionalized MWCNT for simultaneous removal of Pb(2+) ions and eriochrome cyanine R dye after their complexation.

Chitosan (CS) extracted from lobster shells (Persian Gulf, Iran), was grafted with amino functionalized multiwalled carbon nanotube (MWCNT). This novel material was characterized by FE-SEM and FT-IR and used for the ultrasound-assisted removal of Pb(2+) ions and eriochrome cyanine R (ECR) dye. A central composite design (SCCD) under response surface methodology was used for studying the influences of important variables in removal process such as initial ECR and Pb(2+) ions concentrations, adsorbent mass and sonication time on the removal efficiency. Linear, 2FI, quadratic and cubic models were performed and a quadratic model was selected for analysis of each response. ANOVA for the quadratic model shows the F-value parameter (820.44 and 537.12 for ECR and Pb(2+) ions removal, respectively) and very low p-value (<0.0001), implying that the model was highly significant for understudy analytes adsorption. To achieve maximum removal, the optimum condition was determined and were set as:19.34 and 18.20mgL(-1),0.018g and 9.35min for initial ECR and Pb(2+) ion concentrations, adsorbent mass and sonication time, respectively. At these optimum conditions, 97.06% of ECR and 99.29% of Pb(2+) ions were removed in a short time

RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann–Steiner Syndrome

International audienceA growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variants in KMT2A, a gene coding for histone methyltransferase, have been associated with Wiedemann-Steiner syndrome (WSS), a rare developmental disorder mainly characterized by intellectual disability (ID) and hypertrichosis. As KMT2A is known to regulate the expression of multiple target genes through methylation of lysine 4 of histone 3 (H3K4me), we sought to investigate the transcriptomic consequences of KMT2A variants involved in WSS. Using fibroblasts from four WSS patients harboring loss-of-function KMT2A variants, we performed RNA sequencing and identified a number of genes for which transcription was altered in KMT2A-mutated cells compared to the control ones. Strikingly, analysis of the pathways and biological functions significantly deregulated between patients with WSS and healthy individuals revealed a number of processes predicted to be altered that are relevant for hypertrichosis and intellectual disability, the cardinal signs of this disease