High expression of YEATS2 as a predictive factor of poor prognosis in patients with hepatocellular carcinoma.

YEATS domain containing 2 (YEATS2), it may function as a proto-oncogene. This study aims to investigate if YEATS2 correlates with prognosis in hepatocellular carcinoma. The prognostic landscape of YEATS2 and its relationship with expression in hepatocellular carcinoma were deciphered with public databases, RT-qPCR and western-blot in tissue samples. The expression profiling and prognostic value of YEATS2 were explored using UALCAN, TIMER, OncoLnc database. Transcription and survival analyses of YEATS2 in hepatocellular carcinoma were investigated with cBioPortal database. The STRING database was explored to identify molecular functions and signaling pathways downstream of YEATS2. YEATS2 expression was significantly higher in hepatocellular carcinoma compared with adjacent non-malignant tissues. Promoter methylation of YEATS2 exhibited different patterns in hepatocellular carcinoma. High expression of YEATS2 was associated with poorer survival. Mechanistically, YEATS2 was involved in mediating multiple biological processes including morphogenesis and migration.

Insole Systems for Disease Diagnosis and Rehabilitation: A Review.

Some chronic diseases, including Parkinson's disease (PD), diabetic foot, flat foot, stroke, elderly falling, and knee osteoarthritis (KOA), are related to orthopedic organs, nerves, and muscles. The interaction of these three parts will generate a comprehensive result: gait. Furthermore, the lesions in these regions can produce abnormal gait features. Therefore, monitoring the gait features can assist medical professionals in the diagnosis and analysis of these diseases. Nowadays, various insole systems based on different sensing techniques have been developed to monitor gait and aid in medical research. Hence, a detailed review of insole systems and their applications in disease management can greatly benefit researchers working in the field of medical engineering. This essay is composed of the following sections: the essay firstly provides an overview of the sensing mechanisms and parameters of typical insole systems based on different sensing techniques. Then this essay respectively discusses the three stages of gait parameters pre-processing, respectively: pressure reconstruction, feature extraction, and data normalization. Then, the relationship between gait features and pathogenic mechanisms is discussed, along with the introduction of insole systems that aid in medical research; Finally, the current challenges and future trends in the development of insole systems are discussed.

CBX6 Promotes HCC Metastasis Via Transcription Factors Snail/Zeb1-Mediated EMT Mechanism.

PURPOSE: Hepatocellular carcinoma (HCC) is the most common malignant tumor worldwide with high morbidity and mortality rates. We aimed to examine the expression of chromobox 6 (CBX6) in HCC and analyze its correlation with clinicopathological features of HCC patients. Moreover, the role of CBX6 in the HCC cell proliferation, invasion and metastasis and the potential mechanism underlying HCC metastasis were also investigated. METHODS: We used quantitative polymerase chain reaction (qRT-PCR) and Western blot to evaluate the expression levels of CBX6 in HCC cell lines. Furthermore, the expression of CBX6 in HCC and the adjacent non-tumor tissues was assessed by immunohistochemistry (IHC). Cell proliferation was evaluated using MTT assay, cell migration and invasion were measured using wound healing and transwell assays. Finally, we detected the expression of target proteins in HCC cell lines transfected with CBX6 overexpression plasmid or CBX6 shRNA plasmid by Western blot. RESULTS: We found that the expression of CBX6 was increased in 280 cases of HCC tissues compared that in adjacent non-tumor tissues. HCC patients with high CBX6 expression had a higher tendency to have high growth rate, strong invasion ability, high clinical stage and poor tumor differentiation. Functional study demonstrated that the upregulation of CBX6 promotes proliferation, migration and invasion of HCC cells while silencing CBX6 in HCC cells significantly inhibited cell proliferation, migration and invasion. Furthermore, CBX6 could accelerate the EMT process in HCC cells by upregulating the expression of snail and zeb1. CONCLUSION: CBX6 played an important role in the process of tumorigenesis and progression in HCC and enhanced the invasion and metastasis ability of HCC cells through regulating transcription factors snail/zeb1-mediated EMT mechanism, which indicated that the protein could serve as a novel therapeutic target for the treatment of HCC.

The retinoblastoma protein selectively represses E2F1 targets via a TAAC DNA element during cellular senescence.

The retinoblastoma (Rb) protein mediates heterochromatin formation at the promoters of E2 transcription factor 1 (E2F1) target genes, such as proliferating cell nuclear antigen and cyclin A2 (CCNA2), and represses these genes during cellular senescence. However, the selectivity of Rb recruitment is still not well understood. Here, we demonstrate that a senescence-associated gene is a direct target of E2F1 and is also repressed by heterochromatin in senescent cells. In contrast, ARF and p27(KIP1), which are also E2F1 targets, are not repressed by Rb and heterochromatin formation. By comparing the promoter sequences of these genes, we found a novel TAAC element that is present in the cellular senescence-inhibited gene, proliferating cell nuclear antigen, and CCNA2 promoters but absent from the ARF and p27(KIP1) promoters. This TAAC element associates with Rb and is required for Rb recruitment. We further determined that TAAC element-mediated Rb association requires the E2F1 binding site, but not E2F1 protein. These results provide a novel molecular mechanism for the different expression patterns of E2F1 targets and afford new mechanistic insight regarding the selectivity of Rb-mediated heterochromatin formation and gene repression during cellular senescence.

Binding of the JmjC demethylase JARID1B to LSD1/NuRD suppresses angiogenesis and metastasis in breast cancer cells by repressing chemokine CCL14.

JARID1B is a member of the JmjC/ARID family of demethylases that specifically demethylates tri- and di-methylated forms of histone H3 lysine 4 (H3K4) that are associated with active genes. JARID1B expression is dysregulated in several cancers in which it has been implicated, but how it might affect tumor progression is unclear. In this study, we report that JARID1B is a physical component of the LSD1/NuRD complex that functions in transcriptional repression. JARID1B and LSD1 acted in a sequential and coordinated manner to demethylate H3K4. A genome-wide transcriptional analysis revealed that among the cellular signaling pathways targeted by the JARID1B/LSD1/NuRD complex is the CCL14 chemokine pathway of cell migration and angiogenesis. JARID1B repressed the expression of CCL14, an epithelial derived chemokine, suppressing the angiogenic and metastatic potential of breast cancer cells in vivo. Our findings indicate that CCL14 is a critical mediator of the JARID1B/LSD1/NuRD complex in regulation of angiogenesis and metastasis in breast cancer, identifying a novel potential therapeutic target for breast cancer intervention.

Identification of the proliferation/differentiation switch in the cellular network of multicellular organisms.

The protein-protein interaction networks, or interactome networks, have been shown to have dynamic modular structures, yet the functional connections between and among the modules are less well understood. Here, using a new pipeline to integrate the interactome and the transcriptome, we identified a pair of transcriptionally anticorrelated modules, each consisting of hundreds of genes in multicellular interactome networks across different individuals and populations. The two modules are associated with cellular proliferation and differentiation, respectively. The proliferation module is conserved among eukaryotic organisms, whereas the differentiation module is specific to multicellular organisms. Upon differentiation of various tissues and cell lines from different organisms, the expression of the proliferation module is more uniformly suppressed, while the differentiation module is upregulated in a tissue- and species-specific manner. Our results indicate that even at the tissue and organism levels, proliferation and differentiation modules may correspond to two alternative states of the molecular network and may reflect a universal symbiotic relationship in a multicellular organism. Our analyses further predict that the proteins mediating the interactions between these modules may serve as modulators at the proliferation/differentiation switch.