Research

22 pages, 5029 KiB

Open AccessArticle

miRNA Pattern in Hypoxic Microenvironment of Kidney Cancer—Role of PTEN

by Aleksandra Majewska, Klaudia Brodaczewska, Aleksandra Filipiak-Duliban, Arkadiusz Kajdasz and Claudine Kieda

Biomolecules 2022, 12(5), 686; https://doi.org/10.3390/biom12050686 - 11 May 2022

Cited by 5 | Viewed by 2787

Abstract

MicroRNAs are post-transcriptional regulators of gene expression, and disturbances of their expression are the basis of many pathological states, including cancers. The miRNA pattern in the context of tumor microenvironment explains mechanisms related to cancer progression and provides a potential target of modern [...] Read more.

MicroRNAs are post-transcriptional regulators of gene expression, and disturbances of their expression are the basis of many pathological states, including cancers. The miRNA pattern in the context of tumor microenvironment explains mechanisms related to cancer progression and provides a potential target of modern therapies. Here we show the miRNA pattern in renal cancer focusing on hypoxia as a characteristic feature of the tumor microenvironment and dysregulation of PTEN, being a major tumor suppressor. Methods comprised the CRSPR/Cas9 mediated PTEN knockout in the Renca kidney cancer cell line and global miRNA expression analysis in both in vivo and in vitro (in normoxic and hypoxic conditions). The results were validated on human cancer models with distinct PTEN status. The increase in miR-210-3p in hypoxia was universal; however, the hypoxia-induced decrease in PTEN was associated with an increase in miR-221-3p, the loss of PTEN affected the response to hypoxia differently by decreasing miR-10b-5p and increasing miR-206-3p. In turn, the complete loss of PTEN induces miR-155-5p, miR-100-5p. Upregulation of miR-342-3p in knockout PTEN occurred in the context of the whole tumor microenvironment. Thus, effective identification of miRNA patterns in cancers must consider the specificity of the tumor microenvironment together with the mutations of key suppressors. Full article

(This article belongs to the Special Issue MicroRNAs - Small Molecules with Great Potential in Tumorigenesis)

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18 pages, 1612 KiB

Open AccessArticle

A Set of 17 microRNAs Common for Brain and Cerebrospinal Fluid Differentiates Primary Central Nervous System Lymphoma from Non-Malignant Brain Tumors

by Maria Sromek, Grzegorz Rymkiewicz, Agnieszka Paziewska, Lukasz Michal Szafron, Maria Kulecka, Michalina Zajdel, Mariusz Kulinczak, Michalina Dabrowska, Aneta Balabas, Zbigniew Bystydzienski, Magdalena Chechlinska and Jan Konrad Siwicki

Biomolecules 2021, 11(9), 1395; https://doi.org/10.3390/biom11091395 - 21 Sep 2021

Cited by 2 | Viewed by 2390

Abstract

The diagnosis of primary central nervous system (CNS) lymphoma, which is predominantly of the diffuse large B-cell lymphoma type (CNS DLBCL), is challenging. MicroRNAs (miRs) are gene expression-regulating non-coding RNAs that are potential biomarkers. We aimed to distinguish miR expression patterns differentiating CNS [...] Read more.

The diagnosis of primary central nervous system (CNS) lymphoma, which is predominantly of the diffuse large B-cell lymphoma type (CNS DLBCL), is challenging. MicroRNAs (miRs) are gene expression-regulating non-coding RNAs that are potential biomarkers. We aimed to distinguish miR expression patterns differentiating CNS DLBCL and non-malignant CNS diseases with tumor presentation (n-ML). Next generation sequencing-based miR profiling of cerebrospinal fluids (CSFs) and brain tumors was performed. Sample source-specific (CSF vs. brain tumor) miR patterns were revealed. Even so, a set of 17 miRs differentiating CNS DLBCL from n-ML, no matter if assessed in CSF or in a tumor, was identified. Along with the results of pathway analyses, this suggests their pathogenic role in CNS DLBCL. A combination of just four of those miRs (miR-16-5p, miR-21-5p, miR-92a-3p, and miR-423-5p), assessed in CSFs, discriminated CNS DLBCL from n-ML samples with 100% specificity and 67.0% sensitivity. Analyses of paired CSF-tumor samples from patients with CNS DLBCL showed significantly lower CSF levels of miR-26a, and higher CSF levels of miR-15a-5p, miR-15b-5p, miR-19a-3p, miR-106b-3p, miR-221-3p, and miR-423-5p. Noteworthy, the same miRs belonged to the abovementioned set differentiating CNS DLBCL from non-malignant CNS diseases. Our results not only add to the basic knowledge, but also hold significant translational potential. Full article

(This article belongs to the Special Issue MicroRNAs - Small Molecules with Great Potential in Tumorigenesis)

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Review

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27 pages, 1429 KiB

Open AccessReview

Revisiting the miR-200 Family: A Clan of Five Siblings with Essential Roles in Development and Disease

by Vignesh Sundararajan, Ulrike C. Burk and Karolina Bajdak-Rusinek

Biomolecules 2022, 12(6), 781; https://doi.org/10.3390/biom12060781 - 03 Jun 2022

Cited by 8 | Viewed by 2508

Abstract

Over two decades of studies on small noncoding RNA molecules illustrate the significance of microRNAs (miRNAs/miRs) in controlling multiple physiological and pathological functions through post-transcriptional and spatiotemporal gene expression. Among the plethora of miRs that are essential during animal embryonic development, in this [...] Read more.

Over two decades of studies on small noncoding RNA molecules illustrate the significance of microRNAs (miRNAs/miRs) in controlling multiple physiological and pathological functions through post-transcriptional and spatiotemporal gene expression. Among the plethora of miRs that are essential during animal embryonic development, in this review, we elaborate the indispensable role of the miR-200 family (comprising miR-200a, -200b, 200c, -141, and -429) in governing the cellular functions associated with epithelial homeostasis, such as epithelial differentiation and neurogenesis. Additionally, in pathological contexts, miR-200 family members are primarily involved in tumor-suppressive roles, including the reversal of the cancer-associated epithelial–mesenchymal transition dedifferentiation process, and are dysregulated during organ fibrosis. Moreover, recent eminent studies have elucidated the crucial roles of miR-200s in the pathophysiology of multiple neurodegenerative diseases and tissue fibrosis. Lastly, we summarize the key studies that have recognized the potential use of miR-200 members as biomarkers for the diagnosis and prognosis of cancers, elaborating the application of these small biomolecules in aiding early cancer detection and intervention. Full article

(This article belongs to the Special Issue MicroRNAs - Small Molecules with Great Potential in Tumorigenesis)

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19 pages, 655 KiB

Open AccessReview

microRNA-Mediated Encoding and Decoding of Time-Dependent Signals in Tumorigenesis

by Simone Tealdi, Elsi Ferro, Carlo Cosimo Campa and Carla Bosia

Biomolecules 2022, 12(2), 213; https://doi.org/10.3390/biom12020213 - 26 Jan 2022

Viewed by 2737

Abstract

microRNAs, pivotal post-transcriptional regulators of gene expression, in the past decades have caught the attention of researchers for their involvement in different biological processes, ranging from cell development to cancer. Although lots of effort has been devoted to elucidate the topological features and [...] Read more.

microRNAs, pivotal post-transcriptional regulators of gene expression, in the past decades have caught the attention of researchers for their involvement in different biological processes, ranging from cell development to cancer. Although lots of effort has been devoted to elucidate the topological features and the equilibrium properties of microRNA-mediated motifs, little is known about how the information encoded in frequency, amplitude, duration, and other features of their regulatory signals can affect the resulting gene expression patterns. Here, we review the current knowledge about microRNA-mediated gene regulatory networks characterized by time-dependent input signals, such as pulses, transient inputs, and oscillations. First, we identify the general characteristic of the main motifs underlying temporal patterns. Then, we analyze their impact on two commonly studied oncogenic networks, showing how their dysfunction can lead to tumorigenesis. Full article

(This article belongs to the Special Issue MicroRNAs - Small Molecules with Great Potential in Tumorigenesis)

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19 pages, 1191 KiB

Open AccessEditor’s ChoiceReview

The Role of miRNA in Regulating the Fate of Monocytes in Health and Cancer

by Anna Alwani, Aneta Andreasik, Rafał Szatanek, Maciej Siedlar and Monika Baj-Krzyworzeka

Biomolecules 2022, 12(1), 100; https://doi.org/10.3390/biom12010100 - 07 Jan 2022

Cited by 9 | Viewed by 2714

Abstract

Monocytes represent a heterogeneous population of blood cells that provide a link between innate and adaptive immunity. The unique potential of monocytes as both precursors (e.g., of macrophages) and effector cells (as phagocytes or cytotoxic cells) makes them an interesting research and therapeutic [...] Read more.

Monocytes represent a heterogeneous population of blood cells that provide a link between innate and adaptive immunity. The unique potential of monocytes as both precursors (e.g., of macrophages) and effector cells (as phagocytes or cytotoxic cells) makes them an interesting research and therapeutic target. At the site of a tumor, monocytes/macrophages constitute a major population of infiltrating leukocytes and, depending on the type of tumor, may play a dual role as either a bad or good indicator for cancer recovery. The functional activity of monocytes and macrophages derived from them is tightly regulated at the transcriptional and post-transcriptional level. This review summarizes the current understanding of the role of small regulatory miRNA in monocyte formation, maturation and function in health and cancer development. Additionally, signatures of miRNA-based monocyte subsets and the influence of exogenous miRNA generated in the tumor environment on the function of monocytes are discussed. Full article

(This article belongs to the Special Issue MicroRNAs - Small Molecules with Great Potential in Tumorigenesis)

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19 pages, 1175 KiB

Open AccessEditor’s ChoiceReview

miRNA as a Modulator of Immunotherapy and Immune Response in Melanoma

by Mai-Huong Thi Nguyen, Yueh-Hsia Luo, An-Lun Li, Jen-Chieh Tsai, Kun-Lin Wu, Pei-Jung Chung and Nianhan Ma

Biomolecules 2021, 11(11), 1648; https://doi.org/10.3390/biom11111648 - 08 Nov 2021

Cited by 15 | Viewed by 2955

Abstract

Immune checkpoint inhibitors are a promising therapy for the treatment of cancers, including melanoma, that improved benefit clinical outcomes. However, a subset of melanoma patients do not respond or acquire resistance to immunotherapy, which limits their clinical applicability. Recent studies have explored the [...] Read more.

Immune checkpoint inhibitors are a promising therapy for the treatment of cancers, including melanoma, that improved benefit clinical outcomes. However, a subset of melanoma patients do not respond or acquire resistance to immunotherapy, which limits their clinical applicability. Recent studies have explored the reasons related to the resistance of melanoma to immune checkpoint inhibitors. Of note, miRNAs are the regulators of not only cancer progression but also of the response between cancer cells and immune cells. Investigation of miRNA functions within the tumor microenvironment have suggested that miRNAs could be considered as key partners in immunotherapy. Here, we reviewed the known mechanism by which melanoma induces resistance to immunotherapy and the role of miRNAs in immune responses and the microenvironment. Full article

(This article belongs to the Special Issue MicroRNAs - Small Molecules with Great Potential in Tumorigenesis)

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16 pages, 999 KiB

Open AccessEditor’s ChoiceReview

MicroRNAs and Metabolism: Revisiting the Warburg Effect with Emphasis on Epigenetic Background and Clinical Applications

by Zsuzsanna Gaál

Biomolecules 2021, 11(10), 1531; https://doi.org/10.3390/biom11101531 - 17 Oct 2021

Cited by 5 | Viewed by 3546

Abstract

Since the well-known hallmarks of cancer were described by Hanahan and Weinberg, fundamental advances of molecular genomic technologies resulted in the discovery of novel puzzle pieces in the multistep pathogenesis of cancer. MicroRNAs are involved in the altered epigenetic pattern and metabolic phenotype [...] Read more.

Since the well-known hallmarks of cancer were described by Hanahan and Weinberg, fundamental advances of molecular genomic technologies resulted in the discovery of novel puzzle pieces in the multistep pathogenesis of cancer. MicroRNAs are involved in the altered epigenetic pattern and metabolic phenotype of malignantly transformed cells. They contribute to the initiation, progression and metastasis-formation of cancers, also interacting with oncogenes, tumor-suppressor genes and epigenetic modifiers. Metabolic reprogramming of cancer cells results from the dysregulation of a complex network, in which microRNAs are located at central hubs. MicroRNAs regulate the expression of several metabolic enzymes, including tumor-specific isoforms. Therefore, they have a direct impact on the levels of metabolites, also influencing epigenetic pattern due to the metabolite cofactors of chromatin modifiers. Targets of microRNAs include numerous epigenetic enzymes, such as sirtuins, which are key regulators of cellular metabolic homeostasis. A better understanding of reversible epigenetic and metabolic alterations opened up new horizons in the personalized treatment of cancer. MicroRNA expression levels can be utilized in differential diagnosis, prognosis stratification and prediction of chemoresistance. The therapeutic modulation of microRNA levels is an area of particular interest that provides a promising tool for restoring altered metabolism of cancer cells. Full article

(This article belongs to the Special Issue MicroRNAs - Small Molecules with Great Potential in Tumorigenesis)

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Other

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13 pages, 770 KiB

Open AccessSystematic Review

Circulating MicroRNAs as Novel Potential Diagnostic Biomarkers for Osteosarcoma: A Systematic Review

by Thaís Borges Gally, Milena Magalhães Aleluia, Grasiely Faccin Borges and Carla Martins Kaneto

Biomolecules 2021, 11(10), 1432; https://doi.org/10.3390/biom11101432 - 30 Sep 2021

Cited by 4 | Viewed by 1865

Abstract

Osteosarcoma (OS) is a fast-progressing bone tumor with high incidence in children and adolescents. The main diagnostic methods for OS are imaging exams and biopsies. In spite of the several resources available for detecting the disease, establishing an early diagnosis is still difficult, [...] Read more.

Osteosarcoma (OS) is a fast-progressing bone tumor with high incidence in children and adolescents. The main diagnostic methods for OS are imaging exams and biopsies. In spite of the several resources available for detecting the disease, establishing an early diagnosis is still difficult, resulting in worse prognosis and lower survival rates for patients with OS. The identification of novel biomarkers would be helpful, and recently, circulating microRNAs (miRNAs) have been pointed to as possible non-invasive biomarkers. In order to assess the effectiveness of miRNA research, we performed a systematic review to assess the potential role of circulating miRNAs as biomarkers for OS diagnosis. We performed a search in various databases—PubMed, LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde), VHL (Virtual Health Library), Elsevier, Web of Science, Gale Academic One File—using the terms: “Circulating microRNAs” OR “plasma microRNAs” OR “serum microRNAs” OR “blood microRNAs” OR “cell-free microRNAs” OR “exosome microRNAs” OR “extracellular vesicles microRNAs” OR “liquid biopsy” AND “osteosarcoma” AND “diagnostic”. We found 35 eligible studies that were independently identified and had had their quality assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Despite the useful number of publications on this subject and the fact that several microRNAs showed excellent diagnostic performance for OS, the lack of consistency in results suggests that additional prospective studies are needed to confirm the role of circulating miRNAs as non-invasive biomarkers in OS. Full article

(This article belongs to the Special Issue MicroRNAs - Small Molecules with Great Potential in Tumorigenesis)

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