Correlation between SMADs and Colorectal Cancer Expression, Prognosis, and Immune Infiltrates.

Background: In recent years, the incidence and mortality of colorectal cancer (CRC) are increasing, and the 5-year survival rate of advanced metastatic CRC is poor. Small mothers against decapentaplegic (SMAD) superfamily are intracellular signal transduction proteins associated with the development and prognosis of a variety of tumors. At present, no study has systematically analysed the relationship between SMADs and CRC. Methods: Here, R3.6.3 was used to analyse the expression of SMADs in pan-cancer and CRC. Protein expression of SMADs were analysed by Human Protein Atlas (HPA). Gene expression profiling interactive analysis (GEPIA) was used to evaluate the correlation between SMADs and tumor stage in CRC. The effect of R language and GEPIA on prognosis was analysed. Mutation rates of SMADs in CRC were determined by cBioPortal, and potentially related genes were predicted using GeneMANIA. R analysis was used to correlate immune cell infiltration in CRC. Results: Both SMAD1 and SMAD2 were found to be weakly expressed in CRC and correlated with the immune invasion level. SMAD1 was correlated with patient prognosis, and SMAD2 was correlated with tumor stage. SMAD3, SMAD4, and SMAD7 were all expressed at low levels in CRC and associated with a variety of immune cells. SMAD3 and SMAD4 proteins were also expressed at low levels, and SMAD4 had the highest mutation rate. SMAD5 and SMAD6 were overexpressed in CRC, and SMAD6 was also associated with patient overall survival (OS) and CD8+ T cells, macrophages, and neutrophils. Conclusions: Our results reveal innovative and strong evidence that SMADs can be used as biomarkers for the treatment and prognosis of CRC.

Bioinformatics analysis on differentially expressed genes between colorectal adenoma and colorectal adenocarcinoma.

BACKGROUND: Colorectal adenoma (CRA) is the main cause of the progression of Colorectal adenocarcinoma (COAD). Therefore, it is very important to accurately reveal its developmental mechanism. METHODS: Differential expression genes (DEGs) in three microarray datasets were screened using GEO and GEO2R. R packages were used for gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) path enrichment analysis. Hub genes screened by STRING, Cytoscape and CytoHubba were used. R was used for DEGs of hub genes, and Gene Expression Profiling Interactive Analysis (GEPIA2) database was used for prognostic Analysis. R-packet were used to analyze tumor pathology, tumour, lymph-nodes, and metastases (TNM) staging, enrichment, immune invasion and prognosis. RESULTS: Among the 66 genes, including 36 up-regulated and 30 down-regulated genes. Survival analysis showed that COL1A1, COL5A2, COL5A1 and secreted protein acidic and rich in cysteine (SPARC) were associated with disease-free survival in patients. The four genes were related to tumor pathological stage, TNM stage and immune invasion. COL1A1 and COL5A2 were highly expressed in chromatin modification and cellular senescence. Low expression of COL5A1 and SPARC was significantly enriched in neutrophil degranulation and Wp VegfavegFR2 signaling pathways. CONCLUSIONS: Obviously, these four key genes can serve as important targets for early diagnosis, treatment, immunity and prognosis of CRA to COAD.

Multifunctional MXene/Aramid Nanofiber Composite Films for Efficient Electromagnetic Interference Shielding and Repeatable Early Fire Detection.

Rapid development of highly integrated electronic and telecommunication devices has led to urgent demands for electromagnetic interference (EMI) shielding materials that incorporate flame retardancy, and more desirably the early fire detection ability, due to the potential fire hazards caused by heat propagation and thermal failure of the devices during operation. Here, multifunctional flexible films having the main dual functions of high EMI shielding performance and repeatable fire detection ability are fabricated by vacuum filtration of the mixture of MXene and aramid nanofiber (ANF) suspensions. ANFs serve to reinforce MXene films via the formation of hydrogen bonding between the carbonyl groups of ANFs and the hydroxyl groups of MXene. When the ANF content is 20 wt %, the tensile strength of the film is increased from 24.6 MPa for a pure MXene film to 79.5 MPa, and such a composite film (9 µm thickness) exhibits a high EMI shielding effectiveness (SE) value of ∼40 dB and a specific SE (SSE) value of 4361.1 dB/mm. Upon fire exposure, the composite films can trigger the fire detection system within 10 s owing to the thermoelectric property of MXene. The self-extinguishing feature of ANFs ensures the structural integrity of the films during burning, thus allowing for continuous alarm signals. Moreover, the films also exhibit excellent Joule heating and photothermal conversion performances with rapid response and sufficient heating reliability.

Hsa_circ_0031787 promotes cell proliferation and invasion in colorectal cancer.

OBJECTIVE: Circular RNA (circRNA) has been found to be involved in regulating tumor development. However, the roles and underlying mechanisms of circRNA in colorectal cancer (CRC) development remain unclear. In this study, we investigated the effects of hsa_circ_0031787 on CRC.a METHODS: Aberrant circRNA expression was explored by the Gene Expression Omnibus (GEO) database, and hsa_circ_0031787 was selected for further study. Hsa_circ_0031787 expression was determined in CRC tissues and cell lines by qRT-PCR. Cell proliferation was measured by Edu and colony formation assays. Cell invasion was tested by Transwell assays. RESULTS: Hsa_circ_0031787 expression levels in CRC were significantly increased and correlated with advanced TNM stage and lymph node metastasis in CRC patients. Functional assays showed that hsa_circ_0031787 suppression reduced CRC cell proliferation and invasion in vitro and reduced tumor growth in vivo. Furthermore, hsa_circ_0031787 suppression reduced activation of the Wnt/ß-catenin axis in CRC. CONCLUSIONS: Our results showed that hsa_circ_0031787 may function as an oncogenic circRNA in CRC progression, thus providing a new potential therapeutic target.

Silencing of PPMD1 inhibits proliferation of human colon cancer cells via induction of apoptosis and cell cycle arrest.

PURPOSE: Accumulating reports have shown the oncogenic properties of PPMD1 (protein phosphatase, Mg2+/Mn2+ dependent 1D) in different cancer types. This study was undertaken to explore the role and therapeutic potential of PPM1D in colon cancer. METHODS: HT-29 colon cancer cell line was used in this study. Expression analysis of PPMD1 was performed by qRT-PCR. Cell viability was determined by CCK-8 assay. DAPI, acridin orange/ethidium bromide (AO/EB) and propidium iodide (PI)staining assays were used for apoptosis detection. Cell cycle analysis was performed by flow cytometry. Protein expression was determined by western blot analysis. RESULTS: The results showed that the expression of PPMD1 was significantly upregulated in colon cancer by 3.2 to 4.8 fold. Silencing of PPMD1 caused significant decline in the proliferation rate of the HT-29 colon cancer cells that was due to induction of apoptosis as evidenced by DAPI, AO/EB and PI staining. Annexin V/PI showed a significant increase in the percentage of apoptotic of HT-29 cells upon silencing of PPMD1. The induction of apoptosis was also accompanied by increase in Bax and decrease in Bcl-2 expression. PPMD1 silencing also resulted in arrest of the HT-29 cells in the G2/M phase of the cell cycle which was also associated with upsurge of p21 and p53 and depletion of cyclin B1 expression levels. PPMD1 silencing also caused decrease in the viability of the HT-29 cells which was concomitant with suppression of MMP-2 and MMP-9 expression. CONCLUSION: These findings suggest that PPMD1 has oncogenic properties in colon cancer and exhibit therapeutic implications in colon cancer treatment.

The Involvement of NF-κB/Klotho Signaling in Colorectal Cancer Cell Survival and Invasion.

Lipopolysaccharide significantly increased invasion, cell proliferation, and phospho-NF-κB p65 and phospho-IGF-1R protein, but decreased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 cells in SW480 and HT29 colorectal cancer cells. In contrast, NF-κB inhibitor exhibited a counteract effect of lipopolysaccharide. Transfection of Toll-like receptor 4 shRNA significantly decreased phospho-NF-κB p65 and phospho-IGF-1R protein levels, invasion, but significantly increased klotho protein expression, cell apoptosis, and the percentage of sub G0/G1 in SW480 and HT29 cells. In conclusion, inflammation inhibits klotho gene expression in colorectal cancer cells through activation of Toll-like receptor 4 /NF-κB signal pathway.

PPM1D is a prognostic marker and therapeutic target in colorectal cancer.

Protein phosphatase, Mg2+/Mn2+ dependent, 1D (PPM1D) has been associated with carcinogenesis. The present study investigated PPM1D expression as a potential biomarker in colorectal cancer (CRC). PPM1D expression was assessed using immunohistochemistry in 368 patients with CRC. The correlation between PPM1D expression, clinicopathological features and prognosis was analyzed. PPM1D small interfering (si)RNA-induced PPM1D silencing was performed in CRC cell lines to assess the effect of PPM1D on tumor cell proliferation and invasion in vitro. A total of 68.48% (252/368) of the CRC samples displayed high PPM1D expression. By contrast, only 9.24% (34/368) of the matched non-cancerous tissue samples exhibited high PPM1D expression. High PPM1D expression was correlated with node metastasis (P=0.0024), distant metastasis (P<0.001) and TNM stage (P=0.0016). Kaplan-Meier survival analysis revealed that patients with low PPM1D expression had significantly longer survival than those with high PPM1D expression (P=0.012). Moreover, multivariate analyses demonstrated that high PPM1D expression was an independent prognostic factor for overall survival (hazard ratio = 0.24; 95% confidence interval, 0.13-0.86; P=0.004). Furthermore, PPM1D gene silencing was found to significantly reduce the proliferation and invasion of CRC cells in vitro. These findings suggest a role for PPM1D as a prognostic marker and potential therapeutic target in CRC.

[Evolutionary analysis of neuraminidase gene of A/H7N9 influenza virus].

In 2013, the World Health Organization reported the first case of human infection with a new influenza A (H7N9) virus in China. This has caused damage and panic within certain areas in China. Therefore, analysis of this virus with bioinformatics technology is very necessary. Neuraminidase (NA) is one of the most important antigens of the influenza virus and an important target for anti-flu drugs. In this study, the nucleotide and protein sequences of NA gene of A/H7N9 influenza viruses were retrieved from the NCBI database, and MEGA 5.0 software was employed to construct a phylogenetic tree based on the nucleotide coding sequence; BioEdit software was used to align the nucleotide and protein sequences of NA and calculate the homologies of nucleotides and amino acids and then to analyze the important mutation sites of NA gene. The results demonstrated that the spread of influenza virus H7N9 showed certain geographical and temporal relations. The H7N9 virus isolated from China in 2013 belonged to Euroasiatic serotype, and its NA stalk region hadobvious variation, which may be one of the reasons that this virus infects human. These analyses may be very helpful for understanding the evolutionary relationship and mutation trend of A/H7N9 influenza viruses.