Transcriptomic changes associated with DKK4 overexpression in pancreatic cancer cells detected by RNA-Seq

Abstract

The promotion of tumor development by Dickkopf 4 (DKK4) is receiving increased attention. However, the association between DKK4 and pancreatic cancer remains unclear. DKK4 expression was measured in pancreatic ductal adenocarcinoma tissues using qRT-PCR and immunohistochemistry. A DKK4-overexpressing pancreatic cancer cell line was established, and the differentially expressed genes (DEGs) that were induced by DKK4 were identified using transcriptome sequencing. The association between the identified DEGs and pancreatic cancer was assessed using gene ontology (GO), pathway analysis, pathway interaction networks, differentially expressed gene interaction network analysis, and co-expression gene networks. Finally, the accuracy of the analyses was validated using serial paraffin and frozen sections of clinical samples. DKK4 is highly expressed in pancreatic cancer tissues. DEGs of overexpression DKK4 of PANC-1 are mostly upregulated. GO and pathway analysis showed that DKK4 are associated with tumor and organ development and immune inflammation. The mitogen-activated protein kinase (MAPK) signaling pathway was the main signal transduction pathway that showed significant enrichment in overexpression DKK4 of PANC-1. The results of GO, pathway analyses, and differentially expressed gene interaction network identified genes that are closely associated with tumor development, including MAPK3, PIK3R3, VAV3, JAG1, and Notch3. The immunohistochemistry and immunofluorescence results suggested that DKK4 is co-expressed with MAPK3 and VAV3 in pancreatic cancer tissues. The results presented here show for the first time that DKK4 is highly expressed in pancreatic cancer tissues. Bioinformatics analysis of a DKK4-overexpressing of PANC-1 identified several oncogenes that are closely associated with tumors, and the MAPK signaling pathway is the core signal transduction pathway. DKK4 can be co-expressed with MAPK3 and VAV3 in pancreatic ductal adenocarcinoma tissues. Thus, DKK4 may have function on the development and progression of pancreatic cancer.

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Comparison of in vitro antileukemic activity of obatoclax and ABT-737

Abstract

Obatoclax and ABT-737 belong to a new class of anticancer agents known as BH3-mimetics. These agents antagonize the anti-apoptotic members of Bcl-2 family. The Bcl-2 proteins modulate sensitivity of many types of cancer cells to chemotherapy. Therefore, the objective of the present study was to examine and compare the antileukemic activity of obatoclax and ABT-737 applied alone, and in combination with anticancer agent, mafosfamide and daunorubicin. The in vitro cytotoxic effects of the tested agents on human leukemia cells were determined using the spectrophotometric MTT test, Coulter electrical impedance method, flow cytometry annexin V–fluorescein/propidium iodide assay, and light microscopy technique. The combination index analysis was used to quantify the extent of agent interactions. BH3 mimetics significantly decreased the leukemia cell viability and synergistically enhanced the cytotoxic effects induced by mafosfamide and daunorubicin. Obatoclax affected the cell viability to a greater degree than did ABT-737. In addition, various patterns of temporary changes in the cell volume and count, and in the frequency of leukemia cells undergoing apoptosis, were found 24 and 48 h after the tested agent application. ABT-737 combined with anticancer agents induced apoptosis more effectively than obatoclax when given in the same combination regimen. The results of the present study point to the different antileukemic activities of obatoclax and ABT-737, when applied alone, and in combination with anticancer agents. A better understanding of the exact mechanisms of BH3 mimetic action is of key importance for their optional use in cancer therapy.

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The interplay between microRNAs and Twist1 transcription factor: a systematic review

Abstract

Twist1 (also known as Twist) is a transcription factor that belongs to the family of basic helix-loop-helix (bHLH) proteins. It functions as a negative regulator of epithelial gene expression and a positive regulator of mesenchymal gene expression, thereby leading to induction of the epithelial mesenchymal transition (EMT), a process in which epithelial cells acquire the motile and migratory characteristics of mesenchymal cells. In addition to regulating the expression of protein-coding genes, Twist1 regulates the expression of microRNAs (miRNAs), adding a regulatory layer to EMT induction. Interestingly, the mRNA of Twist1 represents a downstream target of miRNAs, indicating an intricate network between miRNAs and Twist1. This network was shown to play multiple roles in cancer cell migration, invasion, and metastasis. The network can induce angiogenesis, protect cells from oncogene-induced apoptosis and senescence, enhance cancer cell resistance to conventional therapies, and increase cancer stem cell (CSC) populations. Recently, miRNAs have attracted considerable attention as potential promising tools in cancer therapies. Thus, this systematic review was conducted to clarify the reciprocal link between Twist1 and miRNAs in order to provide potential candidate miRNAs for diagnostic and therapeutic approaches in cancer treatment.

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Association of toll-like receptor 2 ∆22 and risk for gastric cancer considering main effects and interactions with smoking: a matched case-control study from Mizoram, India

Abstract

Toll-like receptors (TLRs) are evolutionary conserved cell surface receptors of the innate immune system. Smoking has significant immunological effects which are mediated via TLRs on various receptor-mediated innate response pathways. Polymorphisms of TLR genes are associated with susceptibility toward various malignancies. The present study was undertaken to examine the association between TLR2 ∆22 and gastric cancer. In this study, we also investigated the interaction between TLR2 ∆22 and smoking. A total of 133 histologically confirmed gastric cancer cases and 266 age-sex-matched controls were selected for this study. TLR2 ∆22 genotypes were determined by allele-specific polymerase chain reaction (PCR). Binary conditional logistic regression analysis was used to find the association of TLR2 ∆22 with risk of gastric cancer. Logistic regression using hierarchically well-formulated models was used for interaction analysis between smoking and TLR2 ∆22. Persons having TLR2 ∆22 heterozygous genotype had two times increased risk of gastric cancer in multivariate logistic regression model. The interaction analysis using hierarchical logistic regression models between smoking and TLR2 ∆22 by calculating separate X ² for interaction model and only main effect model, the difference of X ² 57.68−47.70 = 9.98 and degrees of freedom (df) 5−3 = 2, revealed significant (α = 0.05, df = 2) omnibus interaction. Our present study revealed TLR2 ∆22 to be significantly and independently associated with gastric cancer risk in Mizoram, and there is also evidence of significant interaction between smoking and TLR2 ∆22 with risk of gastric cancer.

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Hypoxia inducible factor: a potential prognostic biomarker in oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Hypoxia inducible factor (HIF) is involved in many malignant tumors’ growth and metastasis and upregulated by hypoxia, including oral cancer. Many studies have studied about the prognostic value of HIF expression in OSCC; however, they do not get the consistent results. Therefore, this study explored the correlation between the HIF expression and the prognosis of OSCC. It conducted a meta-analysis of relevant publications searched in the Web of Science, PubMed, and ISI Web of Knowledge databases. Totally, this study identified 12 relevant articles reporting a total of 1112 patients. This analysis revealed a significant association between increased risk of mortality (RR = 1.20; 95 % CI 0.74–1.95; I ² 85.4 %) and overexpression of HIFs. Furthermore, different HIF isoforms were associated with overall survival [HIF-1α (RR = 1.18; 95 % CI 0.66–2.11; I ² 87.2 %) and HIF-2α (RR = 1.40; 95 % CI 0.93–2.09; I² 0.0 %)]. These results show that overexpression of HIFs, regardless of whether the HIF-1α or HIF-2α isoforms are overexpressed is significantly associated with increased risk of mortality in OSCC patients. In this study, the funnel is symmetric, suggesting existed no publication bias.

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Tumor suppressor NGX6 inhibits the growth and metastasis of multiple cancers

Abstract

Nasopharyngeal carcinoma-associated gene 6 (NGX6) is a membrane protein primarily located in the nuclear membrane and cell membrane. Several groups reported that NGX6 gene was down-regulated in nasopharyngeal carcinoma (NPC), gastric cancer, lung cancer, liver cancer, and colorectal cancer and even less in the carcinomas with metastasis. Current studies have demonstrated that NGX6 possesses various biological functions, such as regulating protein expression of related genes, involving cell signal transduction pathways, negatively controlling cell cycle progression, inhibiting angiogenesis, and increasing the sensitivity of patients to anti-cancer drugs. Some factors regulating the expression level of NGX6 gene also have been studied. The methylation of promoter of NGX6 and histone H3K9 negatively regulates its expression, similar to the function of transcription factor special protein-1 (Sp1). However, the regulatory factor early growth response gene 1 (Egr-1) is provided with positive regulation function. This review will summarize the progress of those studies on NGX6 and elucidate the potential application of NGX6 for some malignant diseases.

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Colon cancer screening guidelines - STLtoday.com

Colon cancer screening guidelines STLtoday.com My maternal grandmother died of colon cancer, my brother is presently getting chemo for colon cancer, a double cousin had it and my father's double cousin also has had a couple of bouts. ... The tonsils and sinuses are the most likely places for this. and more »

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