scholarly journals Pan-Cancer Analysis of Prognostic and Immune Infiltrates for CXCs

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4153
Author(s):  
Long Li ◽  
Wenchao Yao ◽  
Sen Yan ◽  
Xianghui Dong ◽  
Zhenyi Lv ◽  
...  
Keyword(s):  
Animal Experiments ◽  
Intestinal Flora ◽  
Clinical Samples ◽  
Mrna Levels ◽  
Immune Infiltration ◽  
Pancreatic Cancers ◽  
Multiple Datasets ◽  
Geo Dataset ◽  
Cancer Tissues ◽  
Pan Cancer

Background: CXCs are important genes that regulate inflammation and tumor metastasis. However, the expression level, prognosis value, and immune infiltration of CXCs in cancers are not clear. Methods: Multiple online datasets were used to analyze the expression, prognosis, and immune regulation of CXCs in this study. Network analysis of the Amadis database and GEO dataset was used to analyze the regulation of intestinal flora on the expression of CXCs. A mouse model was used to verify the fact that intestinal bacterial dysregulation can affect the expression of CXCs. Results: In the three cancers, multiple datasets verified the fact that the mRNA expression of this family was significantly different; the mRNA levels of CXCL3, 8, 9, 10, 14, and 17 were significantly correlated with the prognosis of three cancers. CXCs were correlated with six types of immuno-infiltrating cells in three cancers. Immunohistochemistry of clinical samples confirmed that the expression of CXCL8 and 10 was higher in three cancer tissues. Animal experiments have shown that intestinal flora dysregulation can affect CXCL8 and 10 expressions. Conclusion: Our results further elucidate the function of CXCs in cancers and provide new insights into the prognosis and immune infiltration of breast, colon, and pancreatic cancers, and they suggest that intestinal flora may influence disease progression through CXCs.

scholarly journals Integrative Analysis of MUC4 to Prognosis and Immune Infiltration in Pan-Cancer: Friend or Foe?

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao-Peng Gao ◽  
Jie-Jie Dong ◽  
Tian Xie ◽  
Xiaoqing Guan
Keyword(s):  
Genomic Alteration ◽  
Epigenetic Alterations ◽  
Immune Infiltration ◽  
Cancer Pathogenesis ◽  
Appropriate Treatment ◽  
Proliferation And Metastasis ◽  
Cancer Types ◽  
Cancer Tissues ◽  
Pan Cancer ◽  
Tumor Proliferation And Metastasis

MUC4, a transmembrane mucin, plays important roles in epithelial renewal and differentiation. Recent studies suggest that MUC4 has been implicated in pancreatic cancer pathogenesis and is expressed in various normal and cancer tissues. The underlying features of MUC4 across various cancer types may allow us to ensure appropriate treatment and patient monitoring. However, the contributions of MUC4 to pan-cancer have not been well characterized. In this study, we investigated the expression pattern and prognostic value of MUC4 across multiple databases. We further explored genomic and epigenetic alterations of MUC4, its association with proliferation and metastasis, and the correlation with immune infiltration in different cancers. Our results characterized the distinct expression profile and prognostic values of MUC4 in pan-cancer. Through examining its association with genomic alteration, tumor proliferation, and metastasis, as well as tumor infiltration, we revealed multiple function effects of MUC4. MUC4 may influence prognosis, proliferation, metastasis, and immune response in opposite directions. In conclusion, our findings suggested the necessity to more carefully evaluate MUC4 as a biomarker and therapeutic target and develop the new antibodies for cancer detection and intervention.

Development and Validation of a Novel M6A-related LncRNA Prognostic Signature Associated with Immune Microenvironment for Ovarian Serous Cystadenocarcinoma

2021 ◽  
Author(s):  
Rui Geng ◽  
Tian Chen ◽  
Zihang Zhong ◽  
Senmiao Ni ◽  
Jianling Bai ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Cox Regression ◽  
Great Influence ◽  
Clinical Samples ◽  
Consensus Clustering ◽  
Prognostic Signature ◽  
Cancer Stemness ◽  
Gynecological Malignancy ◽  
Pan Cancer ◽  
Geo Database

Abstract Background: OV is the most lethal gynecological malignancy. M6A and lncRNAs have great influence on OV development and patients' immunotherapy response. Here, we decided to establish a reliable signature in the light of mRLs. Method: The lncRNAs associated with m6A in OV were analyzed and obtained by co-expression analysis in the light of TCGA-OV database. Univariate, LASSO and multivariate Cox regression analyses were employed to establish the model in the light of the mRLs. K-M analysis, PCA, GSEA, and nomogram based on the TCGA-OV and GEO database were conducted to prove the predictive value and independence of the model. The underlying relationship between the model and TME and cancer stemness properties were further investigated through immune features comparison, consensus clustering analysis, and Pan-cancer analysis.Results: A prognostic signature comprising four mRLs: WAC-AS1, LINC00997, DNM3OS, and FOXN3-AS1, was constructed and verified for OV according to TCGA and GEO database. The expressions of the four mRLs were confirmed by qRT-PCR in clinical samples. Applying this signature, people can identify patients more effectively. All the sample were assigned into two clusters, and the clusters had different overall survival, clinical features, and tumor microenvironment. Finally, Pan-cancer analysis further demonstrated the four mRLs significantly related to immune infiltration, TME and cancer stemness properties in various cancer types. Conclusion: This study provided an accurate prognostic signature for patients with OV and elucidated the potential mechanism of the mRLs in immune modulation and treatment response, giving new insights into identifying new therapeutic targets.

scholarly journals Tumor-Suppressive MicroRNA-708 Targets Notch1 to Suppress Cell Proliferation and Invasion in Gastric Cancer

2018 ◽  
Vol 26 (9) ◽  
pp. 1317-1326 ◽  
Author(s):  
Xuyan Li ◽  
Xuanfang Zhong ◽  
Xiuhua Pan ◽  
Yan Ji
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Inverse Association ◽  
Novel Target ◽  
Cancer Tissues ◽  
Proliferation And Invasion

Growing evidence has demonstrated that numerous microRNAs (miRNAs) may participate in the regulation of gastric carcinogenesis and progression. This phenomenon suggests that gastric cancer-related miRNAs can be identified as effective therapeutic targets for this disease. miRNA-708 (miR-708) has recently been reported to be aberrantly expressed in several types of cancer and contribute to carcinogenesis and progression. However, the expression level, biological roles, and underlying mechanisms of miR-708 in gastric cancer are poorly understood. Here we found that miR-708 was downregulated in gastric cancer tissues and cell lines. Downregulated miR-708 expression was significantly associated with lymphatic metastasis, invasive depth, and TNM stage. Further investigation indicated that ectopic expression of miR-708 prohibited cell proliferation and invasion in gastric cancer. Bioinformatics analysis showed that Notch1 was a potential target of miR-708. Notch1 was further confirmed as a direct target gene of miR-708 in gastric cancer by dual-luciferase reporter assay, reverse transcription quantitative polymerase chain reaction, and Western blot analysis. Furthermore, an inverse association was found between miR-708 and Notch1 mRNA levels in gastric cancer tissues. In addition, restored Notch1 expression rescued the inhibitory effects on gastric cancer cell proliferation and invasion induced by miR-708 overexpression. Our findings highlight the tumor-suppressive roles of miR-708 in gastric cancer and suggest that miR-708 may be investigated as a novel target for gastric cancer treatment.

scholarly journals Nuclear upregulation of PI3K p110β correlates with increased rRNA transcription in endometrial cancer cells

2019 ◽  
Author(s):  
Fatemeh Mazloumi Gavgani ◽  
Thomas Karlsson ◽  
Ingvild L Tangen ◽  
Andrea Papdiné Morovicz ◽  
Victoria Smith Arnesen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Pi3k Pathway ◽  
Clinical Samples ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Cytoplasmic Staining ◽  
Ec Cells

AbstractGenes encoding for components of the phosphoinositide 3-kinase (PI3K) pathway are frequently mutated in cancer, including inactivating mutations of PTEN and activating mutations of PIK3CA, encoding the PI3K catalytic subunit p110α. PIK3CB, encoding p110β, is rarely mutated, but can contribute to tumourigenesis in some PTEN-deficient tumours. The underlying molecular mechanisms are however poorly understood. By analysing cell lines and annotated clinical samples, we have previously found that p110β is highly expressed in endometrial cancer (EC) cell lines and that PIK3CB mRNA levels increase early in primary tumours correlating with lower survival. Selective inhibition of p110α and p110β led to different effects on cell signalling and cell function, p110α activity being correlated to cell survival in PIK3CA mutant cells and p110β with cell proliferation in PTEN-deficient cells. To understand the mechanisms governing the differential roles of these isoforms, we assessed their sub-cellular localisation. p110α was cytoplasmic whereas p110β was both cytoplasmic and nuclear with increased levels in both compartments in cancer cells. Immunohistochemistry of p110β in clinically annotated patient tumour sections revealed high nuclear/cytoplasmic staining ratio, which correlated significantly with higher grades. Consistently, the presence of high levels of p110β in the nuclei of EC cells, correlated with high levels of its product phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) in the nucleus. Using immunofluorescence labelling, we observed both p110β and PtdIns(3,4,5)P3 in the nucleoli of EC cell lines. The production of nucleolar PtdIns(3,4,5)P3 was dependent upon p110β activity. EC cells with high levels of nuclear PtdIns(3,4,5)P3 and p110β showed elevated nucleolar activity as assessed by the increase in 47S pre-rRNA transcriptional levels in a p110β-dependent manner. Altogether, these results present a nucleolar role for the PI3K pathway that may contribute to tumour progression in endometrial cancer.

scholarly journals Prognostic and immunological value of LTB4R in pan-cancer

2021 ◽  
Vol 18 (6) ◽  
pp. 9336-9356
Author(s):  
Sidan Long ◽  
◽  
Shuangshuang Ji ◽  
Kunmin Xiao ◽  
Peng Xue ◽  
...  
Keyword(s):  
Immune Cells ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Negative Influence ◽  
Leukotriene B4 ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Significant Difference ◽  
Pan Cancer

<abstract> <sec><title>Background</title><p>LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain.</p> </sec> <sec><title>Methods</title><p>We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies.</p> </sec> <sec><title>Results</title><p>In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns.</p> </sec> <sec><title>Conclusion</title><p>The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer.</p> </sec> </abstract>

scholarly journals A simple promoter containing two Sp1 sites controls the expression of sterol-regulatory-element-binding protein 1a (SREBP-1a)

2005 ◽  
Vol 386 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Chengkang ZHANG ◽  
Dong-Ju SHIN ◽  
Timothy F. OSBORNE
Keyword(s):  
Transcriptional Activation ◽  
Binding Protein ◽  
Regulatory Element ◽  
Animal Experiments ◽  
Proximal Region ◽  
Mrna Levels ◽  
Relative Level ◽  
Transcriptional Activation Domain ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

The mammalian gene for SREBP-1 (sterol-regulatory-element-binding protein 1) contains two promoters that control the production of two proteins, SREBP-1a and -1c, and each contains a unique N-terminal transcriptional activation domain, but they are otherwise identical. The relative level of each mRNA varies from tissue to tissue and they respond differently to regulatory stimuli. SREBP-1c is more abundantly expressed in liver, where its level is also regulated by insulin and liver X receptor activators, and it is also autoregulated by SREBPs. In contrast, SREBP-1a mRNA levels are relatively low and constant in different tissues and few studies have specifically analysed its pattern of expression and regulation. In the present study, we show that the promoter for SREBP-1a is contained in a very small promoter-proximal region containing two Sp1 sites. The small and relatively simple structure for its promoter provides an explanation for the low level of SREBP-1a expression. Additionally, since Sp1 has been implicated in the modest regulation of several genes by insulin, its involvement in the expression of the SREBP-1a promoter provides an explanation for the modest insulin regulation observed in animal experiments.

Abstract P207: Role of (Pro)Renin Receptor in the Pathogenesis of Colon Cancer

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Akira Nishiyama ◽  
Juan Wang ◽  
Shinichi Yachida ◽  
Genevieve Nguyen ◽  
Takuo Hirose ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Cell Number ◽  
Ductal Adenocarcinoma ◽  
Mrna Levels ◽  
Protein Levels ◽  
Colon Cancer Cell Lines ◽  
Cancer Tissues

(Pro)renin receptor ((P)RR) is a component of the Wnt receptor complex (Science, 2010). We have recently demonstrated that (P)RR plays an important role in the tumorigenesis of pancreatic ductal adenocarcinoma via the activation of Wnt/β-catenin signaling pathway (Shibayama et al. Sci Rep. 2015). Since the patients with colon cancer often show aberrantly activated Wnt/β-catenin-dependent signaling pathway by the mutations of its components, we investigated the possible role of (P)RR and Wnt/β-catenin signaling pathway in carcinogenesis of colon cancer. Real-time PCR was used for measuring mRNA levels of (P)RR. Protein levels of (P)RR was determined by Western blotting and immunohistochemistry. Activated β-catenin levels were determined by Western blotting. Cell proliferative ability was evaluated by counting the cell number in cultured colon cancer cell lines, HCT116 and DLD-1 cells. As compared to normal colon tissues (n=6), mRNA and protein levels of (P)RR were increased by 2.6- and 2.2-fold, respectively, in colon cancer tissues (n=9), which were associated with increased activated β-catenin levels (by 2.8-fold, P<0.05). However, plasma soluble (P)RR levels were not changed in patients with colon cancer (n=9). (P)RR and activated β-catenin levels were also increased in HCT116 (by 2.2- and 2.7-fold, n=5, respectively) and DLD-1 cells (by 1.9- and 2.8-fold, n=5, respectively). In these cells, inhibiting (P)RR with an siRNA attenuated the activity of β-catenin and reduced the proliferative abilities (n=5, P<0.05, respectively). These data suggest that (P)RR contributes to the tumorigenesis of colon cancer through the activation of Wnt/β-catenin signaling pathway.

scholarly journals Utility of KRAS Gene and Clinicopathological Features in the Assessment of the Risk of Type 2 Diabetes in the Etiology of Colon Cancer

2020 ◽  
Vol 07 (02) ◽  
pp. 035-040
Author(s):  
Wedad Saeed Al-Qahtani ◽  
Ebtesam Al-Olayan ◽  
Fatimah Gh. Albani ◽  
Rania Saad Suliman ◽  
Nada Hamad Aljarba ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Colon Cancer ◽  
Clinicopathological Features ◽  
Mrna Levels ◽  
Kras Gene ◽  
Metastatic Lesions ◽  
Cancer Tissues ◽  
Tremendous Impact

Abstract Background Cancer and diabetes have a tremendous impact on health globally. This study aimed to evaluate the KRAS gene in colon cancer tissues obtained from patients with type 2 diabetes mellitus (T2DM). Materials and Methods Data from 315 cases (156 colon diabetics and 159 patients were nondiabetics) were retrospectively retrieved. mRNA from surgically resected colon cancer tumors were also retrieved. Results The expression of KRAS mRNA was significantly higher in patients afflicted with T2DM than nondiabetic patients. The KRAS mRNA levels were significantly amplified from primary to metastatic lesions (p < 0.001). Conclusion The association between T2DM and colon cancer was well-established in the present study.

Spinal disulfide HMGB1, but not all-thiol HMGB1, induces mechanical hypersensitivity in a TLR4-dependent manner

2015 ◽  
Vol 8 (1) ◽  
pp. 47-47 ◽  
Author(s):  
N.M. Agalave ◽  
S. AbdelMoaty ◽  
P. Lundback ◽  
U. Andersson ◽  
H. Harris ◽  
...  
Keyword(s):  
Intrathecal Injection ◽  
Animal Experiments ◽  
High Mobility ◽  
Disulfide Bridge ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Mechanical Hypersensitivity ◽  
Thiol Form ◽  
Lumbar Spinal ◽  
Deficient Mice

Abstract Aims Increasing evidence indicates that extracellular high mobility group box-1 protein (HMGB1) is involved in the pathogenesis of inflammatory and autoimmune disease. Data from our laboratory demonstrates that HMGB1 contributes to nociceptive behavior in a model of rheumatoid arthritis-induced pain. HMGB1 binds to multiple receptors, including toll like receptor (TLR) 2, TLR4 and receptor for advanced glycation end products (RAGE). When the cysteine in position C106 is in the reduced thiol form and C23 and C45 are engaged in a disulfide bridge (disulfide HMGB1), the molecule functions as a cytokine-inducing TLR4 ligand. In contrast, when these three cysteines are all reduced (all-thiol HMGB1), HMGB1 exclusively potentiates chemotactic activity via CXCR4. It is currently not well understood which receptor and which redox form of HMGB1 that mediates pain hypersensitivity and is therefore the aim of this study. Methods All animal work was carried out in accordance with protocol approved by the local ethics committee for animal experiments in Sweden. Balb/c, C57B/l6 (WT), Tlr2–/–, Tlr4–/– and Rage–/– male mice were used for this study. Disulfide (ds) and all thiol (at) form of HMGB1 were injected intrathecally (1 μg) and mechanical hypersensitivity assessed by von Frey filaments. Lumbar spinal cords were collected after i.t. injection of atHMGB1 and ds HMGB1 and mRNA levels for cytokine and glia markers assessed by quantitative PCR. Results In Balb/c and C57Bl/6 WT mice, i.t injection of dsHMGB1, but not atHMGB1, led to a significant reduction in mechanical thresholds. dsHMGB1 induced mechanical hypersensitivity 6 h after i.t. injection, which lasted for 5 days, compared to i.t. injection of saline. When dsHMGB1 was injected i.t. to Tlr4 deficient mice it did not induce mechanical hypersensitivity. In contrast Tlr2 and Rage deficient mice were still susceptible to dsHMGB1-induced mechanical hypersensitivity. Analysis of mRNA for cytokines and glial cell-associated factors in lumbar spinal cords revealed increased levels of Tnf, Ccl2, Cxcl1, Cxcl2, Gfap and Cd11b in mice injected with dsHMGB1, but not atHMGB1, with exception for Il1β and Cxcr3 that was induced also by atHMGB1. Intrathecal injection of dsHMGB1 to Tlr4–/– deficient mice, did not increase mRNA levels for Tnf, Il1β, Ccl2, Gfap and Cd11b. Conclusions We found the i.t. injection of the disulfide, but not the all-thiol, form of HMGB1 to induce pronouncedand long-lasting mechanical hypersensitivity, glial reactivity and cytokine induction in a TLR4-, but not TLR2- or RAGE-dependent manner. Thus our data indicates that, the redox state of HMGB1 is key for determining its nociceptive property and receptor usage and thus also the functional consequences of HMGB1 release. Agents interfering with extracellular HMGB1 may be considered in the development of new pain relieving therapeutics.

Sign in / Sign up

Export Citation Format

Share Document