The role of extracellular vesicle microRNAs in cancer biology

2017 ◽  
Vol 55 (5) ◽  
Author(s):  
Ryou-u Takahashi ◽  
Marta Prieto-Vila ◽  
Ai Hironaka ◽  
Takahiro Ochiya
Keyword(s):  
Cancer Biology ◽  
Target Genes ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Large Family ◽  
Extracellular Vesicle ◽  
Cancer Development ◽  
Transcriptional Level ◽  
Cellular Mirnas ◽  
Aberrant Expression

AbstractmicroRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Multiple studies report that miRNAs are involved in homeostatic maintenance and that aberrant expression of miRNAs is often observed in various types of diseases, including cancer. In cancer biology, miRNAs exert functional roles in tumor initiation, drug resistance, and metastasis. miRNAs are also secreted through small vesicles called exosomes, which are endosome-derived vesicles derived from various cell types including immune and tumor cells. In addition to cellular miRNAs (ce-miRNAs), secreted miRNAs (se-miRNAs) play important roles in cancer development and metastasis. Therefore, se-miRNAs in body fluids have been investigated as a promising biomarkers and therapeutic targets for cancer treatment. In this review, we summarize the current knowledge of miRNA functions in cancer development and discuss the potential clinical applications of se-miRNAs, e.g. as diagnostic markers and therapeutic targets.

scholarly journals Cross-Kingdom Regulation by Plant microRNAs Provides Novel Insight into Gene Regulation

2020 ◽  
Author(s):  
Abdul Fatah A Samad ◽  
Mohd Farizal Kamaroddin ◽  
Muhammad Sajad
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Current Knowledge ◽  
Circulatory System ◽  
Dietary Therapy ◽  
Transcriptional Level ◽  
Plant Mirnas ◽  
Health Issues ◽  
Plant Mirna ◽  
Potential Applications

ABSTRACT microRNAs (miRNAs) are well known as major players in mammalian and plant genetic systems that act by regulating gene expression at the post-transcriptional level. These tiny molecules can regulate target genes (mRNAs) through either cleavage or translational inhibition. Recently, the discovery of plant-derived miRNAs showing cross-kingdom abilities to regulate mammalian gene expression has prompted exciting discussions among researchers. After being acquired orally through the diet, plant miRNAs can survive in the digestive tract, enter the circulatory system, and regulate endogenous mRNAs. Here, we review current knowledge regarding the cross-kingdom mechanisms of plant miRNAs, related controversies, and potential applications of these miRNAs in dietary therapy, which will provide new insights for plant miRNA investigations related to health issues in humans.

scholarly journals Screening and Functional Analysis of Hub MicroRNAs Related to Tumor Development in Colon Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Dong-Hu Yu ◽  
Wei Li ◽  
Jing-Yu Huang ◽  
Xiao-Ping Liu ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Functional Analysis ◽  
Gene Networks ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Tumor Development ◽  
Therapeutic Targets ◽  
Cancer Development ◽  
Candidate Mirnas ◽  
The Future

Various microRNAs (miRNAs) are of importance in the development of colon cancer, but most of the mechanisms of the miRNAs are still unclear. In order to clarify the hub miRNAs and their roles in colon cancer development, GSE98406 was used to screen hub miRNAs by bioinformatics analysis. 46 DE-miRNAs (14 were upregulated and 32 were downregulated) and 1738 target genes of DE-miRNAs were ascertained. miRNAs-gene-networks and miRNAs-GO-networks were built to get more knowledge about the function of candidate miRNAs. After validation, three miRNAs (miR-17-5p, miR-182-5p and miR-200a-3p) were recognized to be hub miRNAs associated with the progression of colon cancer. More importantly, the hub miRNAs and the putative targets genes might be new diagnostic and therapeutic targets for colon cancer in the future.

scholarly journals New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 164 ◽  
Author(s):  
Stefania Scala ◽  
Crescenzo D’Alterio ◽  
Samantha Milanesi ◽  
Alessandra Castagna ◽  
Roberta Carriero ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Cancer Biology ◽  
Current Knowledge ◽  
Chemotherapy Resistance ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Molecular Alterations ◽  
Whim Syndrome ◽  
C Terminus ◽  
Genomic Landscape

Deciphering the molecular alterations leading to disease initiation and progression is currently crucial to identify the most relevant targets for precision therapy in cancer patients. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Moreover, malignant cells also express a selective repertoire of chemokine receptors that sustain their growth and spread. At present, different cancer types have been shown to overexpress C-X-C chemokine receptor type 4 (CXCR4) and to respond to its ligand C-X-C motif chemokine 12 (CXCL12). The CXCL12/CXCR4 axis influences cancer biology, promoting survival, proliferation, and angiogenesis, and plays a pivotal role in directing migration of cancer cells to sites of metastases, making it a prognostic marker and a therapeutic target. More recently, mutations in the C-terminus of CXCR4 have been identified in the genomic landscape of patients affected by Waldenstrom’s macroglobulinemia, a rare B cell neoplasm. These mutations closely resemble those occurring in Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis (WHIM) syndrome, an immunodeficiency associated with CXCR4 aberrant expression and activity and with chemotherapy resistance in clinical trials. In this review, we summarize the current knowledge on the relevance of CXCR4 mutations in cancer biology, focusing on its importance as predictors of clinical presentation and response to therapy.

scholarly journals miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1790 ◽  
Author(s):  
Marta Sereno ◽  
Mafalda Videira ◽  
Imola Wilhelm ◽  
István A. Krizbai ◽  
Maria Alexandra Brito
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Current Knowledge ◽  
Survival Rates ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Metastatic Cascade ◽  
Physiological Processes ◽  
Breast Cancer Brain Metastasis ◽  
Health And Disease

MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.

scholarly journals Role of miR-10b-5p in the prognosis of breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7728 ◽  
Author(s):  
Junmin Wang ◽  
Yanyun Yan ◽  
Zhiqi Zhang ◽  
Yali Li
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cancer Development ◽  
Clinicopathological Parameters ◽  
Aberrant Expression ◽  
Expression Levels ◽  
Ppi Networks

Breast cancer is the leading cause of cancer-related death in women worldwide. Aberrant expression levels of miR-10b-5p in breast cancer has been reported while the molecular mechanism of miR-10b-5p in tumorigenesis remains elusive. Therefore, this study was aimed to investigate the role of miR-10b-5p in breast cancer and the network of its target genes using bioinformatics analysis. In this study, the expression profiles and prognostic value of miR-10b-5p in breast cancer were analyzed from public databases. Association between miR-10b-5p and clinicopathological parameters were analyzed by non-parametric test. Moreover, the optimal target genes of miR-10b-5p were obtained and their expression patterns were examined using starBase and HPA database. Additionally, the role of these target genes in cancer development were explored via Cancer Hallmarks Analytics Tool (CHAT). The protein–protein interaction (PPI) networks were constructed to further investigate the interactive relationships among these genes. Furthermore, GO, KEGG pathway and Reactome pathway analyses were carried out to decipher functions of these target genes. Results demonstrated that miR-10b-5p was down-regulated in breast cancer and low expression of miR-10b-5p was significantly correlated to worse outcome. Five genes, BIRC5, E2F2, KIF2C, FOXM1, and MCM5, were considered as potential key target genes of miR-10b-5p. As expected, higher expression levels of these genes were observed in breast cancer tissues than in normal tissues. Moreover, analysis from CHAT revealed that these genes were mainly involved in sustaining proliferative signaling in cancer development. In addition, PPI networks analysis revealed strong interactions between target genes. GO, KEGG, and Reactome pathway analysis suggested that these target genes of miR-10b-5p in breast cancer were significantly involved in cell cycle. Predicted target genes were further validated by qRT-PCR analysis in human breast cancer cell line MDA-MB-231 transfected with miR-10b mimic or antisense inhibitors. Taken together, our data suggest that miR-10b-5p functions to impede breast carcinoma progression via regulation of its key target genes and hopefully serves as a potential diagnostic and prognostic marker for breast cancer.

Biological role of miRNA-146a at virus infections. Modern strategy of search of new safe pharmacological agents for treatment

2021 ◽  
Vol 19 (2) ◽  
pp. 145-174
Author(s):  
Petr D. Shabanov ◽  
Vladimir I. Vashchenko
Keyword(s):  
Virus Infection ◽  
Posttranscriptional Regulation ◽  
Target Genes ◽  
Viral Infections ◽  
Current Knowledge ◽  
Recipient Cell ◽  
Viral Disease ◽  
Cellular Mirnas ◽  
Specific Expression ◽  
Regulatory Pathways

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. Here, we review the current knowledge on the interaction between RNA viruses and cellular miRNAs. We also discuss how cell and tissue-specific expression of miRNAs can directly affect viral pathogenesis. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new preventive and therapeutic strategies for medical treatment viral disease, and СOVID-19.

scholarly journals MicroRNA-129 in Human Cancers: from Tumorigenesis to Clinical Treatment

2016 ◽  
Vol 39 (6) ◽  
pp. 2186-2202 ◽  
Author(s):  
Yanping Gao ◽  
Bing Feng ◽  
Siqi Han ◽  
Lu Lu ◽  
Yitian Chen ◽  
...  
Keyword(s):  
Cancer Diagnosis ◽  
Target Genes ◽  
Clinical Treatment ◽  
Transcriptional Level ◽  
Biological Processes ◽  
Aberrant Expression ◽  
Human Cancers ◽  
Diagnosis And Prognosis ◽  
Growing Body ◽  
Underlying Mechanisms

Emerging evidence has shown that microRNAs (miRNAs) play essential roles in regulating human cancers development and progression. However, the underlying mechanisms remain to be further explored. MiRNAs are a class of endogenous, non-coding, 18-24 nucleotide length single-strand RNAs that moderate gene expression primarily at post-transcriptional level. There is a growing body of literature that recognizes the importance of microRNA (miR)-129 during the development of cancers. Aberrant expression of miR-129 has been detected in various types of human cancers and the validated target genes are involved in cancer-related biological processes such as DNA methylation, cell proliferation, apoptosis, cell cycle, and metastasis. In this review, we summarized the roles of miR-129 family members and their target genes in tumorigenesis and clinical treatment of human cancers, highlighting the potential roles of miR-129 as biomarkers for cancer diagnosis and prognosis, and promising tools for cancer treatment.

scholarly journals NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein

2021 ◽  
Vol 10 ◽  
Author(s):  
Hui Guo ◽  
Jianping Zou ◽  
Ling Zhou ◽  
Min Zhong ◽  
Yan He ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Hippo Pathway ◽  
Therapeutic Targets ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Downstream Target ◽  
Tumorigenesis And Progression

The Yes-associated protein (YAP1) is a main effector of the canonical Hippo pathway, which contributes greatly to tumor initiation, progression, and metastasis in multiple cancers, including gastric cancer (GC). Due to limited knowledge of YAP1 upregulation in cancer, it is a great challenge of therapeutic targets toward the Hippo–YAP1 pathway. Here, we identify nucleolar spindle-associated protein 1 (NUSAP1) as a novel binding partner of YAP1. The upregulation of NUSAP1 is associated with unfavorable clinical outcomes in GC patients, and NUSAP1 depletion impairs its oncogenic properties in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 functions as a positive regulator of YAP1 protein stability, thereby inducing the transcription of Hippo pathway downstream target genes, such as CTGF and CYR61. More interestingly, we find that the cancer-promoting effects of NUSAP1 on GC cell growth, migration, and invasion are mainly mediated by YAP1. Furthermore, aberrant expression of NUSAP1 and YAP1 is highly correlated in GC cell lines and tissues. We herein clarify the role of the oncogenic NUSAP1–YAP1 axis in GC tumorigenesis and progression and, therefore, provide novel therapeutic targets for GC treatment.

scholarly journals The Functions and Unique Features of LncRNAs in Cancer Development and Tumorigenesis

2021 ◽  
Vol 22 (2) ◽  
pp. 632
Author(s):  
Kenzui Taniue ◽  
Nobuyoshi Akimitsu
Keyword(s):  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cancer Development ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
The Past ◽  
Cancer Phenotypes ◽  
Coding Potential

Over the past decades, research on cancer biology has focused on the involvement of protein-coding genes in cancer development. Long noncoding RNAs (lncRNAs), which are transcripts longer than 200 nucleotides that lack protein-coding potential, are an important class of RNA molecules that are involved in a variety of biological functions. Although the functions of a majority of lncRNAs have yet to be clarified, some lncRNAs have been shown to be associated with human diseases such as cancer. LncRNAs have been shown to contribute to many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein and RNA. Here we describe the literature regarding the biogenesis and features of lncRNAs. We also present an overview of the current knowledge regarding the roles of lncRNAs in cancer from the view of various aspects of cellular homeostasis, including proliferation, survival, migration and genomic stability. Furthermore, we discuss the methodologies used to identify the function of lncRNAs in cancer development and tumorigenesis. Better understanding of the molecular mechanisms involving lncRNA functions in cancer is critical for the development of diagnostic and therapeutic strategies against tumorigenesis.

scholarly journals Unveiling the ups and downs of miR-205 in physiology and cancer: transcriptional and post-transcriptional mechanisms

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Elena Ferrari ◽  
Paolo Gandellini
Keyword(s):  
Epithelial Cell ◽  
Target Genes ◽  
Cell Function ◽  
Cell Types ◽  
Future Application ◽  
Transcriptional Level ◽  
Aberrant Expression ◽  
Specific Tumor ◽  
And Function ◽  
Different Cell Types

Abstract miR-205 plays important roles in the physiology of epithelia by regulating a variety of pathways that govern differentiation and morphogenesis. Its aberrant expression is frequently found in human cancers, where it was reported to act either as tumor-suppressor or oncogene depending on the specific tumor context and target genes. miR-205 expression and function in different cell types or processes are the result of the complex balance among transcription, processing and stability of the microRNA. In this review, we summarize the principal mechanisms that regulate miR-205 expression at the transcriptional and post-transcriptional level, with particular focus on the transcriptional relationship with its host gene. Elucidating the mechanisms and factors regulating miR-205 expression in different biological contexts represents a fundamental step for a better understanding of the contribution of such pivotal microRNA to epithelial cell function in physiology and disease, and for the development of modulation strategies for future application in cancer therapy.

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