scholarly journals miRNAs as Influencers of Cell–Cell Communication in Tumor Microenvironment

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 220 ◽  
Author(s):  
Ilaria Conti ◽  
Gabriele Varano ◽  
Carolina Simioni ◽  
Ilaria Laface ◽  
Daniela Milani ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cell Communication ◽  
Altered Expression ◽  
Regulate Gene Expression ◽  
Small Noncoding Rnas ◽  
Physiological Processes ◽  
Extracellular Mirnas ◽  
Obesity And Cancer ◽  
Posttranscriptional Level

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer’s disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications.

scholarly journals MicroRNAs as Biomarkers and Therapeutic Targets in Inflammation- and Ischemia-Reperfusion-Related Acute Renal Injury

2020 ◽  
Vol 21 (18) ◽  
pp. 6738
Author(s):  
Yueh-Lin Wu ◽  
Hsiao-Fen Li ◽  
Hsi-Hsien Chen ◽  
Heng Lin
Keyword(s):  
Ischemia Reperfusion ◽  
Control Cell ◽  
Cell Communication ◽  
Kidney Injury ◽  
High Morbidity ◽  
Small Noncoding Rnas ◽  
Exosomal Mirnas ◽  
Extracellular Mirnas ◽  
Mediate Cell

Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such as contrast medium), is identified by an abrupt decline in kidney function and is associated with high morbidity and mortality. Despite decades of efforts, the pathogenesis of AKI remains poorly understood, and effective therapies are lacking. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level to control cell differentiation, development, and homeostasis. Additionally, extracellular miRNAs might mediate cell–cell communication during various physiological and pathological processes. Recently, mounting evidence indicates that miRNAs play a role in the pathogenesis of AKI. Moreover, emerging research suggests that because of their remarkable stability in body fluids, microRNAs can potentially serve as novel diagnostic biomarkers of AKI. Of note, our previous finding that miR-494 is rapidly elevated in urine but not in serum provides insight into the ultimate role of urine miRNAs in AKI. Additionally, exosomal miRNAs derived from stem cells, known as the stem cell secretome, might be a potential innovative therapeutic strategy for AKI. This review aims to provide new data obtained in this field of research. It is hoped that new studies on this topic will not only generate new insights into the pathophysiology of urine miRNAs in AKI but also might lead to the precise management of this fatal disease.

scholarly journals The functional role of exosome microRNAs in lung cancer

2017 ◽  
Vol 12 (1) ◽  
pp. 223-227 ◽  
Author(s):  
Jia Li ◽  
Wenhuan Gong ◽  
Wenfang Zhu ◽  
Xinyu Shao ◽  
Chunxia Zhang
Keyword(s):  
Lung Cancer ◽  
Expression Patterns ◽  
Cell Communication ◽  
Noncoding Rnas ◽  
Cancer Disease ◽  
Regulate Gene Expression ◽  
Small Noncoding Rnas ◽  
Incidence And Mortality ◽  
The Status

AbstractLung cancer causes the highest incidence and mortality rates of cancer disease worldwide. Despite obvious advances in lung cancer research, a better understanding of the disease is urgently needed to improve early detection and correct diagnoses. Exosomes are released from cancer cells and modulate cell-cell communication. Exosomes transfer a wide variety of molecules including microRNAs. MicroRNAs (miRNAs) are single-stranded, small noncoding RNAs that regulate gene expression. Accumulating evidence indicates that miRNA expression patterns represent the status of physiology and disease. The focus of this review is to provide an update on the progress of miRNAs of cancer-derived exosome as potential biomarkers for lung cancer.

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

scholarly journals Coilin enhances phosphorylation and stability of DGCR8 and promotes miRNA biogenesis

2021 ◽  
pp. mbc.E21-05-0225
Author(s):  
Katheryn E. Lett ◽  
Madelyn K. Logan ◽  
Douglas M. McLaurin ◽  
Michael D. Hebert
Keyword(s):  
Noncoding Rnas ◽  
Mature Mirnas ◽  
Cajal Body ◽  
Mirna Biogenesis ◽  
Regulatory Interaction ◽  
Small Noncoding Rnas ◽  
Control Gene Expression ◽  
Processing Steps ◽  
Posttranscriptional Level

MicroRNAs (miRNAs) are ∼22 nt small noncoding RNAs that control gene expression at the posttranscriptional level through translational inhibition and destabilization of their target mRNAs. The biogenesis of miRNAs involves a series of processing steps beginning with cropping of the primary miRNA transcript by the Microprocessor complex, which is comprised of Drosha and DGCR8. Here we report a novel regulatory interaction between the Microprocessor components and coilin, the Cajal Body (CB) marker protein. Coilin knockdown causes alterations in the level of primary and mature miRNAs, let-7a and miR-34a, and their miRNA targets, HMGA2 and Notch1, respectively. We also found that coilin knockdown affects the levels of DGCR8 and Drosha in cells with (HeLa) and without (WI-38) CBs. To further explore the role of coilin in miRNA biogenesis, we conducted a series of co-immunoprecipitation experiments using coilin and DGCR8 constructs, which revealed that coilin and DGCR8 can form a complex. Additionally, our results indicate that phosphorylation of DGCR8, which has been shown to increase protein stability, is impacted by coilin knockdown. Collectively, our results implicate coilin as a member of the regulatory network governing miRNA biogenesis.

scholarly journals Development of MicroRNAs as Potential Therapeutics against Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Noraini Abd-Aziz ◽  
Nur Izyani Kamaruzman ◽  
Chit Laa Poh
Keyword(s):  
Noncoding Rnas ◽  
Cancer Growth ◽  
Cellular Regulation ◽  
Small Noncoding Rnas ◽  
Synthetic Mirnas ◽  
Vital Effects ◽  
Posttranscriptional Level ◽  
Tumor Suppressor Mirnas ◽  
Potential Therapeutics

MicroRNAs (miRNAs) are small noncoding RNAs that function at the posttranscriptional level in the cellular regulation process. miRNA expression exerts vital effects on cell growth such as cell proliferation and survival. In cancers, miRNAs have been shown to initiate carcinogenesis, where overexpression of oncogenic miRNAs (oncomiRs) or reduced expression of tumor suppressor miRNAs has been reported. In this review, we discuss the involvement of miRNAs in tumorigenesis, the role of synthetic miRNAs as either mimics or antagomirs to overcome cancer growth, miRNA delivery, and approaches to enhance their therapeutic potentials.

scholarly journals The Role of Exosomal MicroRNAs in the Tumor Microenvironment of Breast Cancer

2019 ◽  
Vol 20 (16) ◽  
pp. 3884 ◽  
Author(s):  
Qingqing Liu ◽  
Fu Peng ◽  
Jianping Chen
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Breast Tissue ◽  
Cell Communication ◽  
Donor Cell ◽  
Intracellular Location ◽  
Non Coding Rna ◽  
Anti Cancer ◽  
Cell Sources

Breast cancer, ranking first among women’s cancers worldwide, develops from the breast tissue. Study of the breast tissue is, therefore of great significance to the diagnosis and treatment of breast cancer. Exosomes, acting as an effective communicator between cells, are in the ascendant in recent years. One of the most important cargoes contained in the exosomes is microRNAs, belonging to the non-coding RNA family. When the exosomal microRNAs are absorbed into the intracellular location, most of the microRNAs will act as tumor promoters or suppressors by inhibiting the translation process of the target mRNA, thus affecting the behavior of other stromal cells in the tumor microenvironment. At present, growing research focuses on the different types of donor cell sources, their contribution to cancer, miRNA profiling, their biomarker potential, etc. This review aims to state the function of diverse miRNAs in exosomes medicated cell–cell communication and the potency of some specific enriched miRNAs as molecular markers in clinical trials. We also describe the mechanism of anti-cancer compounds through exosomes and the exploration of artificially engineered techniques that lead miRNA-inhibitors into exosomes for therapeutic use.

scholarly journals Obesity, Insulin Resistance, and Colorectal Cancer: Could miRNA Dysregulation Play a Role?

2019 ◽  
Vol 20 (12) ◽  
pp. 2922 ◽  
Author(s):  
Francesca Cirillo ◽  
Cecilia Catellani ◽  
Chiara Sartori ◽  
Pietro Lazzeroni ◽  
Sergio Amarri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Insulin Resistance ◽  
Low Grade ◽  
Regulate Gene Expression ◽  
New Perspective ◽  
Obesity And Cancer ◽  
Low Grade Inflammation ◽  
Regulate Gene

Obesity is associated with insulin resistance and low-grade inflammation. Insulin resistance is a risk factor for cancer. A recent chapter in epigenetics is represented by microRNAs (miRNAs), which post-transcriptionally regulate gene expression. Dysregulated miRNA profiles have been associated with diseases including obesity and cancer. Herein we report dysregulated miRNAs in obesity both in animal models and in humans, and we also document dysregulated miRNAs in colorectal cancer (CRC), as example of an obesity-related cancer. Some of the described miRNAs are found to be similarly dysregulated both in obesity, insulin resistance (IR), and CRC. Thus, we present miRNAs as a potential molecular link between obesity and CRC onset and development, giving a new perspective on the role of miRNAs in obesity-associated cancers.

scholarly journals The Expanding Role of Vesicles Containing Aquaporins

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 179 ◽  
Author(s):  
M Martinez-Ballesta ◽  
Paula Garcia-Ibañez ◽  
Lucía Yepes-Molina ◽  
Juan Rios ◽  
Micaela Carvajal
Keyword(s):  
Environmental Changes ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Living Cells ◽  
Biotechnological Applications ◽  
Future Perspectives ◽  
Physiological Processes ◽  
Communication Processes ◽  
Other Substances

In animals and plants, membrane vesicles containing proteins have been defined as key for biological systems involving different processes such as trafficking or intercellular communication. Docking and fusion of vesicles to the plasma membrane occur in living cells in response to different stimuli, such as environmental changes or hormones, and therefore play an important role in cell homeostasis as vehicles for certain proteins or other substances. Because aquaporins enhance the water permeability of membranes, their role as proteins immersed in vesicles formed of natural membranes is a recent topic of study. They regulate numerous physiological processes and could hence serve new biotechnological purposes. Thus, in this review, we have explored the physiological implications of the trafficking of aquaporins, the mechanisms that control their transit, and the proteins that coregulate the migration. In addition, the importance of exosomes containing aquaporins in the cell-to-cell communication processes in animals and plants have been analyzed, together with their potential uses in biomedicine or biotechnology. The properties of aquaporins make them suitable for use as biomarkers of different aquaporin-related diseases when they are included in exosomes. Finally, the fact that these proteins could be immersed in biomimetic membranes opens future perspectives for new biotechnological applications.

scholarly journals The Role of Exo-miRNAs in Cancer: A Focus on Therapeutic and Diagnostic Applications

2019 ◽  
Vol 20 (19) ◽  
pp. 4687 ◽  
Author(s):  
Francesco Ingenito ◽  
Giuseppina Roscigno ◽  
Alessandra Affinito ◽  
Silvia Nuzzo ◽  
Iolanda Scognamiglio ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Biological Fluids ◽  
Translational Repression ◽  
Regulate Gene Expression ◽  
Physiological Processes ◽  
Non Coding Rna ◽  
Diagnostic Applications ◽  
Tumoral Cells ◽  
Potential Cancer

Exosomes are extracellular vesicles released into biological fluids where they act as carriers of various molecules, including proteins, lipids, and RNAs, between cells, modulating or perturbing specific physiological processes. Recently, it has been suggested that tumoral cells release excessive amounts of exosomes that, through their cargo, promote tumor progression, stimulating growth, angiogenesis, metastasis, insensitivity to chemotherapy, and immune evasion. Increasing evidence highlights exosomal microRNAs (exo-miRNAs) as important players in tumorigenesis. MicroRNA (miRNA) are a class of small non-coding RNA able to regulate gene expression, targeting multiple mRNAs and inducing translational repression and/or mRNA degradation. Exo-miRNAs are highly stable and easily detectable in biological fluids, and for these reasons, miRNAs are potential cancer biomarkers useful diagnostically and prognostically. Furthermore, since exosomes are natural delivery systems between cells, they can be appropriately modified to carry therapeutic miRNAs to specific recipient cells. Here we summarize the main functions of exo-miRNAs and their possible role for diagnostic and therapeutic applications.

scholarly journals Obesity and Cancer Metastasis: Molecular and Translational Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3798
Author(s):  
Stephanie Annett ◽  
Gillian Moore ◽  
Tracy Robson
Keyword(s):  
Adipose Tissue ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Metastatic Tumor ◽  
Established Risk Factor ◽  
Metastatic Behavior ◽  
Obesity And Cancer ◽  
Enhance Tumor Growth

Obesity is a modern health problem that has reached pandemic proportions. It is an established risk factor for carcinogenesis, however, evidence for the contribution of adipose tissue to the metastatic behavior of tumors is also mounting. Over 90% of cancer mortality is attributed to metastasis and metastatic tumor cells must communicate with their microenvironment for survival. Many of the characteristics observed in obese adipose tissue strongly mirror the tumor microenvironment. Thus in the case of prostate, pancreatic and breast cancer and esophageal adenocarcinoma, which are all located in close anatomical proximity to an adipose tissue depot, the adjacent fat provides an ideal microenvironment to enhance tumor growth, progression and metastasis. Adipocytes provide adipokines, fatty acids and other soluble factors to tumor cells whilst immune cells infiltrate the tumor microenvironment. In addition, there are emerging studies on the role of the extracellular vesicles secreted from adipose tissue, and the extracellular matrix itself, as drivers of obesity-induced metastasis. In the present review, we discuss the major mechanisms responsible for the obesity–metastatic link. Furthermore, understanding these complex mechanisms will provide novel therapies to halt the tumor–adipose tissue crosstalk with the ultimate aim of inhibiting tumor progression and metastatic growth.

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