Genomic analyses identify biological processes in ZKSCAN3-deficient colorectal cancer cells

Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3) is associated with cell differentiation, cell proliferation and apoptosis, which has been reported as a critical driver of colorectal cancer. However, the mechanism and function of ZKSCAN3 in colorectal cancer is still unclear. Here, our objective is to identify the functional molecules and signaling by analyzing the RNA-seq data. The GSE172201 was created by the Illumina NovaSeq 6000 (Homo sapiens). The KEGG and GO analyses indicated the immune defense response to virus and transcription activity are major processes in the ZKSCAN3 KO colorectal cancer cells. Moreover, we determined ten key molecules including STAT1, MX1, DDX58, PPARG, EGFR, APP, BST2, DLG4, OASL, and IFIT2. Therefore, our study may provide the novel knowledge of ZKSCAN3 mediated colorectal cancer.

Differential expression of ZSCAN18 in cancer of the vulva.

In these brief notes we document work using published microarray data (1, 2) to pioneer integrative transcriptome analysis comparing vulvar carcinoma to its tissue of origin, the vulva. We report the differential expression of zinc finger and SCAN domain containing 18, encoded by ZSCAN18, in cancer of the vulva. ZSCAN18 may be of pertinence to understanding transformation and disease progression in vulvar cancer (3).

Autoimmune profiling suggests paraneoplastic etiology in pediatric ROHHAD

ROHHAD (Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation) is a rare, yet severe pediatric disorder resulting in hypothalamic dysfunction and frequent sudden death. Genetic and other investigations have failed to identify an etiology or diagnostic test. Frequent co-occurrence of neuroblastic tumors (NTs) and cerebrospinal fluid inflammation point to an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Here, we screened antibodies from a curated cohort of ROHHAD patients (n=9) and controls (n=150) using a programmable phage display of the human peptidome (PhIP-Seq). Our ROHHAD cohort exhibited frequent association with NTs (8/9) and features consistent with autoimmune etiology. Autoantibodies to Zinc finger and SCAN domain-containing protein 1 (ZSCAN1) were discovered and orthogonally validated in 7 of 9 ROHHAD patients, all of whom had NTs, and shown to be absent in non-ROHHAD pediatric patients with NTs. Notably, human ZSCAN1 expression was confirmed in ROHHAD tumor and healthy human hypothalamus. Our results support the notion that tumor-associated ROHHAD is a pediatric PNS, potentially initiated by an immune response to peripheral NT. ZSCAN1 autoantibodies may aid in an accurate diagnosis of ROHHAD, thus providing a means toward early detection and treatment. Lastly, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches in addition to the classical rodent-based approaches for detecting novel PNS subtypes.

Hypermethylation of SCAND3 and Myo1g Gene Are Potential Diagnostic Biomarkers for Hepatocellular Carcinoma

Presently, there is a lack of effective blood-based biomarkers facilitating the diagnosis of hepatocellular carcinoma (HCC). Thus, we aimed to investigate novel methylation markers for HCC diagnosis, and explore relationships between biomarker methylation and clinicopathology of HCC. The methylation status of the SCAN domain containing three (SCAND3) and myosin 1g (Myo1g) genes in HCC cell lines and tissues were detected by digital droplet PCR. The serum SCAND3 and Myo1g methylation levels were analyzed in HCC-afflicted patients and unafflicted controls. The results indicated SCAND3 and Myo1g methylation were abnormally high in the HCC cell lines and tissues. The values of serum SCAND3, Myo1g, and SCAND3 + Myo1g methylation with respect to facilitating the detection, and early detection of HCC were better than for alpha-fetoprotein (AFP) alone. Furthermore, when we combined SCAND3 + Myo1g with AFP, a high sensitivity and specificity resulted. Notably, in the AFP-negative HCC group, the methylation of SCAND3 and Myo1g also showed an excellent diagnostic performance. Besides this, a high serum SCAND3 methylation level was an independent risk factor for predicting portal vein tumor thrombus (PVTT) in HCC patients (OR = 4.746, p = 0.013). Finally, SCAND3 and Myo1g enhanced the HCC diagnostics as noninvasive serum methylation biomarkers, and the SCAND3 methylation status effectively indicated HCC accompanied by PVTT.

Zscan4c activates endogenous retrovirus MERVL and cleavage embryo genes

Endogenous retroviruses (ERVs) contribute to ∼10 percent of the mouse genome. They are often silenced in differentiated somatic cells but differentially expressed at various embryonic developmental stages. A minority of mouse embryonic stem cells (ESCs), like 2-cell cleavage embryos, highly express ERV MERVL. However, the role of ERVs and mechanism of their activation in these cells are still poorly understood. In this study, we investigated the regulation and function of the stage-specific expressed ERVs, with a particular focus on the totipotency marker MT2/MERVL. We show that the transcription factor Zscan4c functions as an activator of MT2/MERVL and 2-cell/4-cell embryo genes. Zinc finger domains of Zscan4c play an important role in this process. In addition, Zscan4c interacts with MT2 and regulates MT2-nearby 2-cell/4-cell genes through promoting enhancer activity of MT2. Furthermore, MT2 activation is accompanied by enhanced H3K4me1, H3K27ac, and H3K14ac deposition on MT2. Zscan4c also interacts with GBAF chromatin remodelling complex through SCAN domain to further activate MT2 enhancer activity. Taken together, we delineate a previously unrecognized regulatory axis that Zscan4c interacts with and activates MT2/MERVL loci and their nearby genes through epigenetic regulation.