A comprehensive review of online resources for microRNA–diseases associations: the state of the art

2021 ◽  
Author(s):  
Maryam Mahjoubin-Tehran ◽  
Samaneh Rezaei ◽  
Amin Jalili ◽  
Amirhossein Sahebkar ◽  
Seyed Hamid Aghaee-Bakhtiari
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Therapy Response ◽  
Clinical Applications ◽  
Significant Development ◽  
Diagnosis And Prognosis ◽  
Mrna Targets ◽  
Disease Information ◽  
Therapeutic Tools ◽  
The Relationship

Abstract MicroRNAs (miRNAs) as small 19- to 24-nucleotide noncoding RNAs regulate several mRNA targets and signaling pathways. Therefore, miRNAs are considered key regulators in cellular pathways as well as various pathologies. There is substantial interest in the relationship between disease and miRNAs, which made that one of the important research topics. Interestingly, miRNAs emerged as an attractive approach for clinical application, not only as biomarkers for diagnosis and prognosis or in the prediction of therapy response but also as therapeutic tools. For these purposes, the identification of crucial miRNAs in disease is very important. Databases provided valuable experimental and computational miRNAs–disease information in an accessible and comprehensive manner, such as miRNA target genes, miRNA related in signaling pathways and miRNA involvement in various diseases. In this review, we summarized miRNAs–disease databases in two main categories based on the general or specific diseases. In these databases, researchers could search diseases to identify critical miRNAs and developed that for clinical applications. In another way, by searching particular miRNAs, they could recognize in which disease these miRNAs would be dysregulated. Despite the significant development that has been done in these databases, there are still some limitations, such as not being updated and not providing uniform and detailed information that should be resolved in future databases. This survey can be helpful as a comprehensive reference for choosing a suitable database by researchers and as a guideline for comparing the features and limitations of the database by developer or designer. Short abstract We summarized miRNAs–disease databases that researchers could search disease to identify critical miRNAs and developed that for clinical applications. This survey can help choose a suitable database for researchers.

scholarly journals Current Research Progress of the Role of LncRNA LEF1-AS1 in a Variety of Tumors

2021 ◽  
Vol 9 ◽  
Author(s):  
Qingyuan Zheng ◽  
Xiao Yu ◽  
Menggang Zhang ◽  
Shuijun Zhang ◽  
Wenzhi Guo ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Malignant Tumors ◽  
Underlying Mechanism ◽  
Research Progress ◽  
Diagnosis And Prognosis ◽  
Binding Factor ◽  
Non Coding Rnas ◽  
The Relationship

Long non-coding RNAs (lncRNA), as key regulators of cell proliferation and death, are involved in the regulation of various processes in the nucleus and cytoplasm, involving biological developmental processes in the fields of immunology, neurobiology, cancer, and stress. There is great scientific interest in exploring the relationship between lncRNA and tumors. Many researches revealed that lymph enhancer-binding factor 1-antisense RNA 1 (LEF1-AS1), a recently discovered lncRNA, is downregulated in myeloid malignancy, acting mainly as a tumor suppressor, while it is highly expressed and carcinogenic in glioblastoma (GBM), lung cancer, hepatocellular carcinoma (HCC), osteosarcoma, colorectal cancer (CRC), oral squamous cell carcinoma (OSCC), prostatic carcinoma, retinoblastoma, and other malignant tumors. Furthermore, abnormal LEF1-AS1 expression was associated with tumorigenesis, development, survival, and prognosis via the regulation of target genes and signaling pathways. This review summarizes the existing data on the expression, functions, underlying mechanism, relevant signaling pathways, and clinical significance of LEF1-AS1 in cancer. It is concluded that LEF1-AS1 can serve as a novel biomarker for the diagnosis and prognosis of various tumors, thus deserves further attention in the future.

scholarly journals Research Progress of miRNA Regulating Cell Signaling Pathways Related to Hepatocarcinogenesis

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Dan Wang ◽  
Xingwu Yang ◽  
Guotai Wang
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Malignant Tumors ◽  
Research Progress ◽  
Biological Processes ◽  
Tumor Cell Proliferation ◽  
Invasion And Metastasis ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
Cell Signaling Pathways

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice. The pathogenesis of HCC is still unclear. Currently, the clinical treatment of HCC is poorly targeted and the therapeutic effect is poor. MicroRNAs (miRNAs) are closely related to the occurrence of HCC, and they are mainly involved in the occurrence and development of HCC through binding to target genes or acting on related signaling pathways. In recent years, studies have shown that miRNA can be used as a potential biomarker for diagnosis and prognosis of HCC. In addition, studies have also shown that miRNA plays a tumor-suppressing or tumor-promoting role in the process of HCC by regulating the biological processes of tumor cell proliferation, migration, invasion and metastasis. In this paper, the recent studies on miRNA signaling pathways related to the occurrence and development of HCC were reviewed, with a view to providing ideas for the clinical diagnosis and treatment of HCC.

scholarly journals The Roles of MicroRNA in Lung Cancer

2019 ◽  
Vol 20 (7) ◽  
pp. 1611 ◽  
Author(s):  
Kuan-Li Wu ◽  
Ying-Ming Tsai ◽  
Chi-Tun Lien ◽  
Po-Lin Kuo ◽  
and Jen-Yu Hung
Keyword(s):  
Lung Cancer ◽  
Cancer Biology ◽  
Genetic Research ◽  
Clinical Applications ◽  
The Past ◽  
Diagnosis And Prognosis ◽  
Lung Cancer Diagnosis ◽  
Therapeutic Development ◽  
And Behavior ◽  
The Relationship

Lung cancer is the most devastating malignancy in the world. Beyond genetic research, epigenomic studies—especially investigations of microRNAs—have grown rapidly in quantity and quality in the past decade. This has enriched our understanding about basic cancer biology and lit up the opportunities for potential therapeutic development. In this review, we summarize the involvement of microRNAs in lung cancer carcinogenesis and behavior, by illustrating the relationship to each cancer hallmark capability, and in addition, we briefly describe the clinical applications of microRNAs in lung cancer diagnosis and prognosis. Finally, we discuss the potential therapeutic use of microRNAs in lung cancer.

HPV-associated penile cancer: Impact of copy number alterations in miRNA/mRNA interactions and potential druggable targets

2021 ◽  
pp. 1-14
Author(s):  
Jenilson da Silva ◽  
Leudivan Nogueira ◽  
Ronald Coelho ◽  
Amanda Deus ◽  
André Khayat ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Copy Number ◽  
Drug Targets ◽  
Penile Cancer ◽  
Target Genes ◽  
Kegg Pathways ◽  
Mrna Targets ◽  
Genome Wide ◽  
Target Treatment ◽  
Druggable Targets

BACKGROUND: Penile cancer (PeCa) is a rare disease, but its incidence has increased worldwide, mostly in HPV+ patients. Nevertheless, there is still no targeted treatment for this carcinoma. OBJECTIVE: To predict the main signaling pathways involved in penile tumorigenesis and its potential drug targets. METHODS: Genome-wide copy number profiling was performed in 28 PeCa. Integration analysis of CNAs and miRNAs and mRNA targets was performed by DIANA-TarBase v.8. The potential impact of the miRNAs/target genes on biological pathways was assessed by DIANA-miRPath v.3.0. For each miRNA, KEGG pathways were generated based on the tarbase and microT-CDS algorithms. Pharmaco-miR was used to identify associations between miRNAs and their target genes to predict druggable targets. RESULTS: 269 miRNAs and 2,395 genes were mapped in cytobands with CNAs. The comparison of the miRNAs mapped at these cytobands and the miRNAs that were predicted to regulate the genes also mapped in these regions, resulted in a set of common 35 miRNAs and 292 genes. Enrichment pathway revealed their involvement in five top signaling pathways. EGFR and COX2 were identified as potential druggable targets. CONCLUSION: Our data indicate the potential use of EGFR and COX2 inhibitors as a target treatment for PeCa patients.

scholarly journals Wnt/β-catenin signaling as a useful therapeutic target in hepatoblastoma

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Ying-Li Sha ◽  
Shuang Liu ◽  
Wen-Wen Yan ◽  
Bo Dong
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Pharmacological Agents ◽  
Ample Evidence ◽  
Diagnosis And Prognosis ◽  
Neurokinin 1 ◽  
Factor Α

Abstract Hepatoblastoma is a malignant tumor in the liver of children that generally occurs at the age of 2–3 years. There have been ample evidence from the preclinical as well as clinical studies suggesting the activation of Wnt/β-catenin signaling in hepatoblastoma, which is mainly attributed to the somatic mutations in the exon 3 of β-catenin gene. There is increased translocation of β-catenin protein from the cell surface to cytoplasm and nucleus and intracellular accumulation is directly linked to the severity of the cancer. Accordingly, the alterations in β-catenin and its target genes may be used as markers in the diagnosis and prognosis of pediatric live tumors. Furthermore, scientists have reported the therapeutic usefulness of inhibition of Wnt/β-catenin signaling in hepatoblastoma and this inhibition of signaling has been done using different methods including short interfering RNA (siRNA), miRNA and pharmacological agents. Wnt/β-catenin works in association with other signaling pathways to induce the development of hepatoblastoma including Yes-associated protein (YAP)1 (YAP-1), mammalian target of rapamycin (mTOR) 1 (mTOR-1), SLC38A1, glypican 3 (GPC3), nuclear factor κ-light-chain-enhancer of activated B cells (NF-kB), epidermal growth factor receptor, ERK1/2, tumor necrosis factor-α (TNF-α), regenerating islet-derived 1 and 3 α (REG1A and 3A), substance P (SP)/neurokinin-1 receptor and PARP-1. The present review describes the key role of Wnt/β-catenin signaling in the development of hepatoblastoma. Moreover, the role of other signaling pathways in hepatoblastoma in association with Wnt/β-catenin has also been described.

scholarly journals MicroRNAs as New Players for Diagnosis, Prognosis, and Therapeutic Targets in Breast Cancer

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Enders K. O. Ng ◽  
Chris L. P. Wong ◽  
Edmond S. K. Ma ◽  
Ava Kwong
Keyword(s):  
Breast Cancer ◽  
Tumor Development ◽  
Therapy Response ◽  
Therapeutic Strategies ◽  
Clinical Applications ◽  
Cancer Prognosis ◽  
Human Breast ◽  
Mrna Targets ◽  
Important Relationship ◽  
Lines Of Evidence

MicroRNAs are small nonprotein-coding RNAs that regulate the expressions of a wide variety of genes by sequence-specific base pairing on the UTR of mRNA targets resulting in mRNA degradation or inhibition of translation. Aberrant expressions of miRNAs have been linked to tumor development, metastasis, diagnosis, prognosis, and therapy response in human breast cancer. Some miRNAs have been considered to have potential clinical applications as a tool for breast cancer prognosis and therapy. Here we describe and discuss lines of evidence supporting the important relationship between miRNAs and breast cancer, and its therapeutic strategies.

MicroRNAs and their role in hematological malignant diseases

2012 ◽  
Vol 153 (52) ◽  
pp. 2051-2059 ◽  
Author(s):  
Zsuzsanna Gaál ◽  
Éva Oláh
Keyword(s):  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Cancer Tissue ◽  
Altered Expression ◽  
Diagnosis And Prognosis ◽  
Oncologic Patients ◽  
Different Types ◽  
Non Coding Rnas ◽  
Success Of Treatment ◽  
Posttranscriptional Level

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.

scholarly journals The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1465 ◽  
Author(s):  
Christiaan J. Stavast ◽  
Stefan J. Erkeland
Keyword(s):  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Small Rnas ◽  
Target Genes ◽  
Biological Functions ◽  
Rnase Iii ◽  
Mrna Targets ◽  
Argonaute Proteins ◽  
Epigenetic Modifiers ◽  
Encoding Genes

MicroRNAs (miRNAs) are critical regulators of gene expression. As miRNAs are frequently deregulated in many human diseases, including cancer and immunological disorders, it is important to understand their biological functions. Typically, miRNA-encoding genes are transcribed by RNA Polymerase II and generate primary transcripts that are processed by RNase III-endonucleases DROSHA and DICER into small RNAs of approximately 21 nucleotides. All miRNAs are loaded into Argonaute proteins in the RNA-induced silencing complex (RISC) and act as post-transcriptional regulators by binding to the 3′- untranslated region (UTR) of mRNAs. This seed-dependent miRNA binding inhibits the translation and/or promotes the degradation of mRNA targets. Surprisingly, recent data presents evidence for a target-mediated decay mechanism that controls the level of specific miRNAs. In addition, several non-canonical miRNA-containing genes have been recently described and unexpected functions of miRNAs have been identified. For instance, several miRNAs are located in the nucleus, where they are involved in the transcriptional activation or silencing of target genes. These epigenetic modifiers are recruited by RISC and guided by miRNAs to specific loci in the genome. Here, we will review non-canonical aspects of miRNA biology, including novel regulators of miRNA expression and functions of miRNAs in the nucleus.

scholarly journals The Multifaceted Roles of USP15 in Signal Transduction

2021 ◽  
Vol 22 (9) ◽  
pp. 4728
Author(s):  
Tanuza Das ◽  
Eun Joo Song ◽  
Eunice EunKyeong Kim
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Cellular Networks ◽  
Clinical Applications ◽  
Regulatory Mechanisms ◽  
Signaling Networks ◽  
Post Translational Modification ◽  
Comprehensive Overview ◽  
E3 Ligases ◽  
Disease Markers

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator.

scholarly journals Reduced Endothelin-2 and Hypoxic Signaling Pathways in Granulosa-Lutein Cells of PCOS Women

2021 ◽  
Vol 22 (15) ◽  
pp. 8216
Author(s):  
Magdalena Szymanska ◽  
Ketan Shrestha ◽  
Eliezer Girsh ◽  
Avi Harlev ◽  
Iris Eisenberg ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Hypoxic Response ◽  
Transfected Cells ◽  
Healthy Women ◽  
Periovulatory Follicles

Granulosa-lutein cells (GLCs) from PCOS women display reduced HIF-1α and EDN2 levels, suggesting their role in PCOS etiology. Here, we investigated the mechanisms involved in aberrant EDN2 expression in PCOS, and its association with HIF-1α. Various HIF-1α-dependent factors were studied in GLCs from PCOS and compared to normally ovulating women. MicroRNA-210 (miR-210), its target genes (SDHD and GPD1L), and HIF-1α-responsive genes (EDN2 and VEGFA) differed in GLCs from PCOS, compared with those of healthy women. Levels of miR-210—designated hypoxiamiR—and EDN2 were reduced in the PCOS GLCs; concomitantly, GPD1L and SDHD levels were elevated. Cultured GLCs retained low EDN2 expression and had low HIF-1α levels, providing evidence for a disrupted hypoxic response in the PCOS GLCs. However, VEGFA expression was elevated in these cells. Next, miR-210 levels were manipulated. miR-210-mimic stimulated EDN2 twice as much as the miR-NC-transfected cells, whereas miR-210-inhibitor diminished EDN2, emphasizing the importance of hypoxiamiR for EDN2 induction. Intriguingly, VEGFA transcripts were reduced by both miR-210-mimic and -inhibitor, demonstrating that EDN2 and VEGFA are distinctly regulated. Disrupted hypoxic response in the GLCs of periovulatory follicles in PCOS women may play a role in ovulation failure, and in the reduced fertility prevalent in this syndrome.

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