scholarly journals Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 1857
Author(s):  
Maria Magdalena Barreca ◽  
Chiara Zichittella ◽  
Riccardo Alessandro ◽  
Alice Conigliaro
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Biological Activities ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Low Oxygen ◽  
Master Regulators ◽  
Signalling Transduction ◽  
Non Coding Rnas ◽  
Multiple Levels

Hypoxia, a characteristic of the tumour microenvironment, plays a crucial role in cancer progression and therapeutic response. The hypoxia-inducible factors (HIF-1α, HIF-2α, and HIF-3α), are the master regulators in response to low oxygen partial pressure, modulating hypoxic gene expression and signalling transduction pathways. HIFs’ activation is sufficient to change the cell phenotype at multiple levels, by modulating several biological activities from metabolism to the cell cycle and providing the cell with new characteristics that make it more aggressive. In the past few decades, growing numbers of studies have revealed the importance of non-coding RNAs (ncRNAs) as molecular mediators in the establishment of hypoxic response, playing important roles in regulating hypoxic gene expression at the transcriptional, post-transcriptional, translational, and posttranslational levels. Here, we review recent findings on the different roles of hypoxia-induced ncRNAs in cancer focusing on the data that revealed their involvement in tumour growth.

scholarly journals Long noncoding RNAs: fine-tuners hidden in the cancer signaling network

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shanshan Zhao ◽  
Xue Zhang ◽  
Shuo Chen ◽  
Song Zhang
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Biological Activities ◽  
Noncoding Rnas ◽  
Fine Tuning ◽  
Multiple Perspectives ◽  
Sequencing Technology ◽  
Protein Coding ◽  
Abnormal Signal ◽  
Non Coding Rnas

AbstractWith the development of sequencing technology, a large number of long non-coding RNAs (lncRNAs) have been identified in addition to coding genes. LncRNAs, originally considered as junk RNA, are dysregulated in various types of cancer. Although protein-coding signaling pathways underlie various biological activities, and abnormal signal transduction is a key trigger and indicator for tumorigenesis and cancer progression, lncRNAs are sparking keen interest due to their versatile roles in fine-tuning signaling pathways. We are just beginning to scratch the surface of lncRNAs. Therefore, despite the fact that lncRNAs drive malignant phenotypes from multiple perspectives, in this review, we focus on important signaling pathways modulated by lncRNAs in cancer to demonstrate an up-to-date understanding of this emerging field.

The Role of miR-210 in the Biological System: A Current Overview

2019 ◽  
Vol 84 (6) ◽  
pp. 233-239
Author(s):  
Xu Hui ◽  
Hisham Al-Ward ◽  
Fahmi Shaher ◽  
Chun-Yang Liu ◽  
Ning Liu
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Low Oxygen ◽  
Cellular Functions ◽  
Regulate Gene Expression ◽  
System A ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation ◽  
A Current

<b><i>Background:</i></b> MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. <b><i>Summary:</i></b> miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. <b><i>Key Message:</i></b> miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.

scholarly journals Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA

Oncogenesis ◽  
2020 ◽  
Vol 9 (9) ◽  
Author(s):  
Guofang Chen ◽  
Binya Liu ◽  
Shasha Yin ◽  
Shuangdi Li ◽  
Yu’e Guo ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Mrna Levels ◽  
Hypoxic Conditions ◽  
Inducing Factors ◽  
Tumour Initiation

Abstract Endometrial cancer stem cells (ECSCs) are stem-like cells endowed with self-renewal and differentiation abilities, and these cells are essential for cancer progression in endometrial cancer (EC). As hallmarks of the tumour microenvironment (TME), hypoxia and hypoxia-inducing factors (HIFs) give rise to the dysregulation of tumour stemness genes, such as SOX2. Against this backdrop, we investigated the regulatory mechanisms regulated by HIFs and SOX2 in ECSCs during EC development. Here, ECSCs isolated from EC cell lines and tissues were found to express stemness genes (CD133 and aldehyde dehydrogenase, ALDH1) following the induction of their ECSC expansion. Notably, m6A methylation of RNA and HIF-1α/2α-dependent AlkB homologue 5 (ALKBH5) participate in the regulation of HIFs and SOX2 in EC, as confirmed by the observations that mRNA levels of m6A demethylases and ALKBH5 significantly increase under hypoxic conditions in ECSCs. Moreover, hypoxia and high ALKBH5 levels restore the stem-like state of differentiated ECSCs and increase the ECSC-like phenotype, whereas the knockdown of HIFs or ALKBH5 significantly reduces their tumour initiation capacity. In addition, our findings validate the role of ALKBH5 in promoting SOX2 transcription via mRNA demethylation, thereby maintaining the stem-like state and tumorigenicity potential of ECSCs. In conclusion, these observations demonstrate a critical role for m6A methylation-mediated regulation of the HIF-ALKBH5-SOX2 axis during ECSC expansion in hypoxic TMEs.

scholarly journals Gene Expression Signatures of a Preclinical Mouse Model during Colorectal Cancer Progression under Low-Dose Metronomic Chemotherapy

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 49
Author(s):  
Hung Ho-Xuan ◽  
Gerhard Lehmann ◽  
Petar Glazar ◽  
Foivos Gypas ◽  
Norbert Eichner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Mouse Model ◽  
Cancer Progression ◽  
Metronomic Chemotherapy ◽  
Circular Rnas ◽  
Primary Tumors ◽  
Non Coding Rnas ◽  
Chemotherapeutic Treatment ◽  
Colorectal Cancer Progression

Understanding the molecular signatures of colorectal cancer progression under chemotherapeutic treatment will be crucial for the success of future therapy improvements. Here, we used a xenograft-based mouse model to investigate, how whole transcriptome signatures change during metastatic colorectal cancer progression and how such signatures are affected by LDM chemotherapy using RNA sequencing. We characterized mRNAs as well as non-coding RNAs such as microRNAs, long non-coding RNAs and circular RNAs in colorectal-cancer bearing mice with or without LDM chemotherapy. Furthermore, we found that circZNF609 functions as oncogene, since over-expression studies lead to an increased tumor growth while specific knock down results in smaller tumors. Our data represent novel insights into the relevance of non-coding and circRNAs in colorectal cancer and provide a comprehensive resource of gene expression changes in primary tumors and metastases. In addition, we present candidate genes that could be important modulators for successful LDM chemotherapy.

scholarly journals Novel Insights Linking lncRNAs and Metabolism With Implications for Cardiac Regeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Magda Correia ◽  
Bruno Bernardes de Jesus ◽  
Sandrina Nóbrega-Pereira
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Metabolic Pathways ◽  
Cardiac Regeneration ◽  
Developed Countries ◽  
Anaerobic Glycolysis ◽  
Metabolic Signaling ◽  
Master Regulators ◽  
Carbohydrate And Lipid Metabolism ◽  
Non Coding Rnas

Heart disease is the leading cause of mortality in developed countries. The associated pathology is typically characterized by the loss of cardiomyocytes that leads, eventually, to heart failure. Although conventional treatments exist, novel regenerative procedures are warranted for improving cardiac regeneration and patients well fare. Whereas following injury the capacity for regeneration of adult mammalian heart is limited, the neonatal heart is capable of substantial regeneration but this capacity is lost at postnatal stages. Interestingly, this is accompanied by a shift in the metabolic pathways and energetic fuels preferentially used by cardiomyocytes from embryonic glucose-driven anaerobic glycolysis to adult oxidation of substrates in the mitochondria. Apart from energetic sources, metabolites are emerging as key regulators of gene expression and epigenetic programs which could impact cardiac regeneration. Long non-coding RNAs (lncRNAs) are known master regulators of cellular and organismal carbohydrate and lipid metabolism and play multifaceted functions in the cardiovascular system. Still, our understanding of the metabolic determinants and pathways that can promote cardiac regeneration in the injured hearth remains limited. Here, we will discuss the emerging concepts that provide evidence for a molecular interplay between lncRNAs and metabolic signaling in cardiovascular function and whether exploiting this axis could provide ground for improved regenerative strategies in the heart.

scholarly journals Network-Based Approaches to Explore Complex Biological Systems towards Network Medicine

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 437 ◽  
Author(s):  
Giulia Fiscon ◽  
Federica Conte ◽  
Lorenzo Farina ◽  
Paola Paci
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Detection Algorithm ◽  
Cell Phenotype ◽  
Disease Genes ◽  
Network Medicine ◽  
Topological Properties ◽  
Systematic Analysis ◽  
Ppi Networks ◽  
Non Coding Rnas

Network medicine relies on different types of networks: from the molecular level of protein–protein interactions to gene regulatory network and correlation studies of gene expression. Among network approaches based on the analysis of the topological properties of protein–protein interaction (PPI) networks, we discuss the widespread DIAMOnD (disease module detection) algorithm. Starting from the assumption that PPI networks can be viewed as maps where diseases can be identified with localized perturbation within a specific neighborhood (i.e., disease modules), DIAMOnD performs a systematic analysis of the human PPI network to uncover new disease-associated genes by exploiting the connectivity significance instead of connection density. The past few years have witnessed the increasing interest in understanding the molecular mechanism of post-transcriptional regulation with a special emphasis on non-coding RNAs since they are emerging as key regulators of many cellular processes in both physiological and pathological states. Recent findings show that coding genes are not the only targets that microRNAs interact with. In fact, there is a pool of different RNAs—including long non-coding RNAs (lncRNAs) —competing with each other to attract microRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The framework of regulatory networks provides a powerful tool to gather new insights into ceRNA regulatory mechanisms. Here, we describe a data-driven model recently developed to explore the lncRNA-associated ceRNA activity in breast invasive carcinoma. On the other hand, a very promising example of the co-expression network is the one implemented by the software SWIM (switch miner), which combines topological properties of correlation networks with gene expression data in order to identify a small pool of genes—called switch genes—critically associated with drastic changes in cell phenotype. Here, we describe SWIM tool along with its applications to cancer research and compare its predictions with DIAMOnD disease genes.

scholarly journals Missing Links in Epithelial-Mesenchymal Transition: Long Non-Coding RNAs Enter the Arena

2017 ◽  
Vol 44 (4) ◽  
pp. 1665-1680 ◽  
Author(s):  
Lei Wang ◽  
Fan Yang ◽  
Lin-Tao Jia ◽  
An-Gang Yang
Keyword(s):  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Biological Activities ◽  
Carcinoma Cells ◽  
Mesenchymal Transition ◽  
Master Regulators ◽  
A Cell ◽  
Non Coding Rnas ◽  
Biological Program

Cancer metastasis occurs through a series of sequential steps, which involves dissemination of tumor cells from a primary site and colonization in distant tissues. To promote the invasion-metastasis cascade, carcinoma cells usually initiate a cell-biological program called epithelial-mesenchymal transition (EMT), which is orchestrated by a set of master regulators, including TGF-β, Snail, ZEB and Twist families. The biological activities of these molecules are tightly regulated by a variety of cell-intrinsic pathways as well as extracellular cues. Recently, accumulating evidence indicates that long non-coding RNAs (lncRNAs) represent some of the most differentially expressed transcripts between primary and metastatic cancers. LncRNAs including MALAT1, HOTAIR, H19, LncRNA-ATB, and LincRNA-ROR have been reported to be involved in the process of EMT, mainly through cross-talking with master regulators of EMT. Thus, understanding the different and precise molecular mechanisms by which functional lncRNAs switch EMT on and off is important for opening up new avenues in lncRNA-directed diagnosis, prognosis, and therapeutic intervention against cancer.

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre
Keyword(s):  
Gene Expression ◽  
Thiamine Deficiency ◽  
Glucose Transporter ◽  
Neuroblastoma Cell ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Vitamin B1 ◽  
Low Oxygen ◽  
Glucose Transporter 1 ◽  
Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

IS tRNA DRIVING BREAST CANCER PROGRESSION?

2019 ◽  
Author(s):  
Zil-e- Rubab
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Developing Countries ◽  
Molecular Mechanism ◽  
Cancer Progression ◽  
Critical Review ◽  
Driving Forces ◽  
Treatment Modalities ◽  
Critical Research ◽  
Research Article

This critical research periodical is mainly based on critical review of research article titled ‘Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression published in Cell by Goodarzi et al1. According to Globocan, 2008 report2, breast is among the leading site of new cancer cases and deaths (691,300/268,900) in females of developing countries and second leading site in USA (Globocan, 2012)3. The extensive research is in progress on different aspects of molecular mechanism of driving forces and different treatment modalities to ease this burden. The above mentioned research article is also part of this effort.

scholarly journals Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kalifa Manjang ◽  
Shailesh Tripathi ◽  
Olli Yli-Harja ◽  
Matthias Dehmer ◽  
Galina Glazko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Progression ◽  
Disease Etiology ◽  
Signature Genes ◽  
Biological Meaning ◽  
Gene Sets ◽  
Breast Cancer Outcome ◽  
Biological Interpretation ◽  
Pathological Behavior

AbstractThe identification of prognostic biomarkers for predicting cancer progression is an important problem for two reasons. First, such biomarkers find practical application in a clinical context for the treatment of patients. Second, interrogation of the biomarkers themselves is assumed to lead to novel insights of disease mechanisms and the underlying molecular processes that cause the pathological behavior. For breast cancer, many signatures based on gene expression values have been reported to be associated with overall survival. Consequently, such signatures have been used for suggesting biological explanations of breast cancer and drug mechanisms. In this paper, we demonstrate for a large number of breast cancer signatures that such an implication is not justified. Our approach eliminates systematically all traces of biological meaning of signature genes and shows that among the remaining genes, surrogate gene sets can be formed with indistinguishable prognostic prediction capabilities and opposite biological meaning. Hence, our results demonstrate that none of the studied signatures has a sensible biological interpretation or meaning with respect to disease etiology. Overall, this shows that prognostic signatures are black-box models with sensible predictions of breast cancer outcome but no value for revealing causal connections. Furthermore, we show that the number of such surrogate gene sets is not small but very large.

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