scholarly journals MOUSSE: Multi-Omics Using Subject-Specific SignaturEs

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3423
Author(s):  
Giuseppe Fiorentino ◽  
Roberto Visintainer ◽  
Enrico Domenici ◽  
Mario Lauria ◽  
Luca Marchetti
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Differential Survival ◽  
Regulatory Processes ◽  
Omics Integration ◽  
Classification Score ◽  
Subject Specific ◽  
The Subject ◽  
Informative Content ◽  
Molecular Bases

High-throughput technologies make it possible to produce a large amount of data representing different biological layers, examples of which are genomics, proteomics, metabolomics and transcriptomics. Omics data have been individually investigated to understand the molecular bases of various diseases, but this may not be sufficient to fully capture the molecular mechanisms and the multilayer regulatory processes underlying complex diseases, especially cancer. To overcome this problem, several multi-omics integration methods have been introduced but a commonly agreed standard of analysis is still lacking. In this paper, we present MOUSSE, a novel normalization-free pipeline for unsupervised multi-omics integration. The main innovations are the use of rank-based subject-specific signatures and the use of such signatures to derive subject similarity networks. A separate similarity network was derived for each omics, and the resulting networks were then carefully merged in a way that considered their informative content. We applied it to analyze survival in ten different types of cancer. We produced a meaningful clusterization of the subjects and obtained a higher average classification score than ten state-of-the-art algorithms tested on the same data. As further validation, we extracted from the subject-specific signatures a list of relevant features used for the clusterization and investigated their biological role in survival. We were able to verify that, according to the literature, these features are highly involved in cancer progression and differential survival.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

scholarly journals TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
You Shuai ◽  
Zhonghua Ma ◽  
Weitao Liu ◽  
Tao Yu ◽  
Changsheng Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

scholarly journals Interleukin-33-Enhanced CXCR4 Signaling Circuit Mediated by Carcinoma-Associated Fibroblasts Promotes Invasiveness of Head and Neck Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3442
Author(s):  
Yu-Chun Lin ◽  
Wen-Yen Huang ◽  
Tsai-Yu Lee ◽  
Yi-Ming Chang ◽  
Su-Feng Chen ◽  
...  
Keyword(s):  
Head And Neck ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Disease Free Survival ◽  
Interleukin 33 ◽  
Cxcr4 Signaling ◽  
Regulatory Circuit ◽  
Carcinoma Associated Fibroblasts ◽  
Self Production

Despite recent advances, treatment for head and neck squamous cell carcinoma (HNSCC) has limited efficacy in preventing tumor progression. We confirmed previously that carcinoma-associated fibroblasts (CAF)-induced interleukin-33 (IL-33) contributed to cancer progression. However, the molecular mechanisms underlying the complex communication network of the tumor microenvironment merited further evaluation. To simulate the IL-33-induced autocrine signaling, stable clones of IL-33-overexpressing HNSCC cells were established. Besides well-established IL-33/ST2 and SDF1/CXCR4 (stromal-derived factor 1/C-X-C motif chemokine receptor 4) signaling, the CAF-induced IL-33 upregulated CXCR4 via cancer cell induction of IL-33 self-production. The IL-33-enhanced-CXCR4 regulatory circuit involves SDF1/CXCR4 signaling activation and modulates tumor behavior. An in vivo study confirmed the functional role of IL-33/CXCR4 in tumor initiation and metastasis. The CXCR4 and/or IL-33 blockade reduced HNSCC cell aggressiveness, with attenuated invasions and metastases. Immunohistochemistry confirmed that IL-33 and CXCR4 expression correlated significantly with disease-free survival and IL-33-CXCR4 co-expression predicted a poor outcome. Besides paracrine signaling, the CAF-induced IL-33 reciprocally enhanced the autocrine cancer-cell self-production of IL-33 and the corresponding CXCR4 upregulation, leading to the activation of SDF1/CXCR4 signaling subsequent to cancer progression. Thus, targeting the IL-33-enhanced-CXCR4 regulatory circuit attenuates tumor aggressiveness and provides a potential therapeutic option for improving the prognosis in HNSCC patients.

scholarly journals Disentangling general achievement levels and subject-specific strengths and weaknesses in mathematics, reading, and science

2020 ◽  
Author(s):  
Olesya Gladushyna ◽  
Rolf Strietholt ◽  
Isa Steinmann
Keyword(s):  
Reading Literacy ◽  
Performance Levels ◽  
Fourth Grade Students ◽  
Subject Specific ◽  
The Subject ◽  
Overall Performance ◽  
Cross Country ◽  
And Gender ◽  
Mathematics And Science ◽  
Achievement Levels

AbstractThe paper uses data from the combined TIMSS (Trends in International Mathematics and Science Study) and PIRLS (Progress in International Reading Literacy Study) assessment in 2011 to explore the subject-specific strengths and weaknesses among fourth grade students worldwide. Previous research came to the conclusion that students only differed in overall achievement levels and did not exhibit subject-specific strengths and weaknesses. This research did, however, not control for differences in overall performance levels when searching for profile differences. Therefore, the present study uses factor mixture analysis to study qualitatively different performance profiles in mathematics, reading, and science while controlling for differences in performance levels. Our findings suggest that the majority of students do not show pronounced strengths and weaknesses and differ mainly in performance levels across mathematics, reading, and science. At the same time, a smaller share of students does indeed show pronounced subject-specific strengths and weaknesses. This result does not represent an artefact, but we find clear and theory-conforming associations between the identified profiles and covariates. We find evidence for cross-country differences in the frequency of subject-specific strengths and weaknesses and gender differences, as well as differences between students who do not or only sometimes speak the language of test at home.

scholarly journals PCGF1 promotes epigenetic activation of stemness markers and colorectal cancer stem cell enrichment

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Guangyu Ji ◽  
Wenjuan Zhou ◽  
Jingyi Du ◽  
Juan Zhou ◽  
Dong Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Tumour Progression ◽  
Stem Cell Markers ◽  
Epigenetic Regulator ◽  
Cell Enrichment ◽  
Histone Trimethylation

AbstractColorectal cancer (CRC) stem cells are resistant to cancer therapy and are therefore responsible for tumour progression after conventional therapy fails. However, the molecular mechanisms underlying the maintenance of stemness are poorly understood. In this study, we identified PCGF1 as a crucial epigenetic regulator that sustains the stem cell-like phenotype of CRC. PCGF1 expression was increased in CRC and was significantly correlated with cancer progression and poor prognosis in CRC patients. PCGF1 knockdown inhibited CRC stem cell proliferation and CRC stem cell enrichment. Importantly, PCGF1 silencing impaired tumour growth in vivo. Mechanistically, PCGF1 bound to the promoters of CRC stem cell markers and activated their transcription by increasing the H3K4 histone trimethylation (H3K4me3) marks and decreasing the H3K27 histone trimethylation (H3K27me3) marks on their promoters by increasing expression of the H3K4me3 methyltransferase KMT2A and the H3K27me3 demethylase KDM6A. Our findings suggest that PCGF1 is a potential therapeutic target for CRC treatment.

scholarly journals Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression

2021 ◽  
Vol 22 (7) ◽  
pp. 3571
Author(s):  
Bonglee Kim ◽  
Ji-Eon Park ◽  
Eunji Im ◽  
Yongmin Cho ◽  
Jinjoo Lee ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Clinical Implications ◽  
Research Perspectives ◽  
Current Review ◽  
Gold Silver ◽  
Significant Efficacy ◽  
Rapid Clearance

Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.

scholarly journals Splicing Genomics Events in Cervical Cancer: Insights for Phenotypic Stratification and Biomarker Potency

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 130
Author(s):  
Flavia Zita Francies ◽  
Sheynaz Bassa ◽  
Aristotelis Chatziioannou ◽  
Andreas Martin Kaufmann ◽  
Zodwa Dlamini
Keyword(s):  
Cervical Cancer ◽  
Alternative Splicing ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapy Resistance ◽  
Splicing Factors ◽  
Aberrant Splicing ◽  
Molecular Alteration ◽  
Common Cancer ◽  
Potential Biomarkers

Gynaecological cancers are attributed to the second most diagnosed cancers in women after breast cancer. On a global scale, cervical cancer is the fourth most common cancer and the most common cancer in developing countries with rapidly increasing mortality rates. Human papillomavirus (HPV) infection is a major contributor to the disease. HPV infections cause prominent cellular changes including alternative splicing to drive malignant transformation. A fundamental characteristic attributed to cancer is the dysregulation of cellular transcription. Alternative splicing is regulated by several splicing factors and molecular changes in these factors lead to cancer mechanisms such as tumour development and progression and drug resistance. The serine/arginine-rich (SR) proteins and heterogeneous ribonucleoproteins (hnRNPs) have prominent roles in modulating alternative splicing. Evidence shows molecular alteration and expression levels in these splicing factors in cervical cancer. Furthermore, aberrant splicing events in cancer-related genes lead to chemo- and radioresistance. Identifying clinically relevant modifications in alternative splicing events and splicing variants, in cervical cancer, as potential biomarkers for their role in cancer progression and therapy resistance is scrutinised. This review will focus on the molecular mechanisms underlying the aberrant splicing events in cervical cancer that may serve as potential biomarkers for diagnosis, prognosis, and novel drug targets.

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