MiRNA Deregulation Distinguishes Anaplastic Thyroid Carcinoma (ATC) and Supports Upregulation of Oncogene Expression

Anaplastic thyroid carcinoma (ATC) is the most fatal and rapidly evolving endocrine malignancy invading the head and neck region and accounts for up to 50% of thyroid cancer-associated deaths. Deregulation of the microRNA (miRNA) expression promotes thyroid carcinoma progression by modulating the reorganization of the ATC transcriptome. Here, we applied comparative miRNA–mRNA sequencing on a cohort of 28 thyroid carcinomas to unravel the association of deregulated miRNA and mRNA expression. This identified 85 miRNAs significantly deregulated in ATC. By establishing a new analysis pipeline, we unraveled 85 prime miRNA–mRNA interactions supporting the downregulation of candidate tumor suppressors and the upregulation of bona fide oncogenes such as survivin (BIRC5) in ATC. This miRNA-dependent reprogramming of the ATC transcriptome provided an mRNA signature comprising 65 genes sharply distinguishing ATC from other thyroid carcinomas. The validation of the deregulated protein expression in an independent thyroid carcinoma cohort demonstrates that miRNA-dependent oncogenes comprised in this signature, the transferrin receptor TFRC (CD71) and the E3-ubiquitin ligase DTL, are sharply upregulated in ATC. This upregulation is sufficient to distinguish ATC even from poorly differentiated thyroid carcinomas (PDTC). In sum, these findings provide new diagnostic tools and a robust resource to explore the key miRNA–mRNA regulation underlying the progression of thyroid carcinoma.

Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer’s Disease

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.

Regulatory Role of microRNAs Targeting the Transcription Co-Factor ZNF521 in Normal Tissues and Cancers

Powerful bioinformatics tools have provided a wealth of novel miRNA–transcription factor networks crucial in controlling gene regulation. In this review, we focus on the biological functions of miRNAs targeting ZNF521, explaining the molecular mechanisms by which the dysregulation of this axis contributes to malignancy. ZNF521 is a stem cell-associated co-transcription factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells. The aberrant expression of ZNF521 transcripts, frequently associated with miRNA deregulation, has been detected in several tumors including pancreatic, hepatocellular, gastric, bladder transitional cell carcinomas as well as in breast and ovarian cancers. miRNA expression profiling tools are currently identifying a multitude of miRNAs, involved together with oncogenes and TFs in the regulation of oncogenesis, including ZNF521, which may be candidates for diagnostic and prognostic biomarkers of cancer.

Lack of Conserved miRNA Deregulation in HPV-Induced Squamous Cell Carcinomas

Squamous cell carcinomas (SCCs) in the anogenital and head and neck regions are associated with high-risk types of human papillomaviruses (HR-HPV). Deregulation of miRNA expression is an important contributor to carcinogenesis. This study aimed to pinpoint commonly and uniquely deregulated miRNAs in cervical, anal, vulvar, and tonsillar tumors of viral or non-viral etiology, searching for a common set of deregulated miRNAs linked to HPV-induced carcinogenesis. RNA was extracted from tumors and nonmalignant tissues from the same locations. The miRNA expression level was determined by next-generation sequencing. Differential expression of miRNAs was calculated, and the patterns of miRNA deregulation were compared between tumors. The total of deregulated miRNAs varied between tumors of different locations by two orders of magnitude, ranging from 1 to 282. The deregulated miRNA pool was largely tumor-specific. In tumors of the same location, a low proportion of miRNAs were exclusively deregulated and no deregulated miRNA was shared by all four types of HPV-positive tumors. The most significant overlap of deregulated miRNAs was found between tumors which differed in location and HPV status (HPV-positive cervical tumors vs. HPV-negative vulvar tumors). Our results imply that HPV infection does not elicit a conserved miRNA deregulation in SCCs.

Transcriptome analysis of arterial and venous circulating miRNAs during hypertension

Most current circulating miRNA biomarkers are derived from peripheral venous blood, whereas miRNA deregulation in arterial blood in disease conditions has been largely ignored. To explore whether peripheral venous blood miRNAs could represent a bona fide specific miRNA deregulation pattern, we selected hypertension, a disease that is particularly associated with vessels, as the model. Circulating miRNA profiles of arterial and venous blood from spontaneously hypertensive (SHR) rats and their corresponding controls (i.e., WKY rats) were investigated by next-generation miRNA sequencing. Little miRNAs were observed between arterial and venous circulating miRNAs in WKY rats. Interestingly, this number was enhanced in SHR hypertensive rats. Bioinformatical analysis of disease association, enriched target genes and the regulatory transcription factors of these differentially expressed miRNAs implied a potential functional link with cardiovascular disease-related functions. Comparisons between arterial and venous miRNAs in hypertension-versus-control conditions also revealed prominent disease association of circulating miRNAs and their target genes in arteries but not in veins. Moreover, a young non-hypertensive animal model in SHR background (i.e. JSHR) was used as a second control for SHR. Additional transcriptomic analysis and droplet digital PCR validation of arterial and venous deregulated miRNAs among SHR and its two controls (WKY, JSHR) revealed a noticeable consensus of artery-deregulated miRNAs in hypertension and two novel arterial circulating signatures (miR-455-3p and miR-140-3p) of hypertension. These results suggest the necessity of re-evaluating the efficacy of certain venous miRNAs identified in previous studies as potential biomarkers in cardiovascular diseases or a wider disease spectrum.

Roles of miRNA dysregulation in the pathogenesis of multiple myeloma

Multiple myeloma (MM) is a malignant disease of plasma cells with complex pathology, causing significant morbidity due to its end-organ destruction. The outcomes of patients with myeloma have significantly improved in the past couple of decades with the introduction of novel agents, such as proteasome inhibitors, immunomodulators, and monoclonal antibodies. However, MM remains incurable and presents considerable individual heterogeneity. MicroRNAs (miRNAs) are short, endogenous noncoding RNAs of 19–22 nucleotides that regulate gene expression at the posttranscriptional level. Numerous studies have shown that miRNA deregulation is closely related to MM pathology, including tumor initiation, progression, metastasis, prognosis, and drug response, which make the complicated miRNA network an attractive and marvelous area of investigation for novel anti-MM therapeutic approaches. Herein, we mainly summarized the current knowledge on the roles of miRNAs, which are of great significance in regulating pathological factors involved in MM progressions, such as bone marrow microenvironment, methylation, immune regulation, genomic instability, and drug resistance. Meanwhile, their potential as novel prognostic biomarkers and therapeutic targets was also discussed.

The biological and diagnostic roles of MicroRNAs in meningiomas

MicroRNAs (miRNAs) refer to a class of small endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level. Emerging studies have shown that miRNAs play critical roles in tumorigenesis and cancer progression. However, roles and mechanisms of miRNA dysregulation in the pathogenesis of meningioma are not fully understood. Here, we first reviewed existing research of aberrantly expressed miRNAs identified by high throughput microarray profiling in meningioma. We also explored the potential of miRNA as biomarkers and therapeutic targets for novel treatment paradigms of meningiomas. In addition, we summarized recent researches that focused on the possible mechanisms involved in miRNA-mediate meningioma occurrence and progression. This review provides an overview of miRNA deregulation in meningioma and indicates the potential of miRNAs to be used as biomarkers or novel therapeutic targets.

Insight toward the MicroRNA Profiling of Laryngeal Cancers: Biological Role and Clinical Impact

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous disease arising from various anatomical locations including the larynx, is a leading cause of death worldwide. Despite advances in multimodality treatment, the overall survival rate of the disease is still largely dismal. Early and accurate diagnosis of HNSCC is urgently demanded in order to prevent cancer progression and to improve the quality of the patient’s life. Recently, microRNAs (miRNAs), a family of small non-coding RNAs, have been widely reported as new robust tools for prediction, diagnosis, prognosis, and therapeutic approaches of human diseases. Abnormally expressed miRNAs are strongly associated with cancer development, resistance to chemo-/radiotherapy, and metastatic potential through targeting a large variety of genes. In this review, we summarize on the recent reports that emphasize the pivotal biological roles of miRNAs in regulating carcinogenesis of HNSCC, particularly laryngeal cancer. In more detail, we report the characterized miRNAs with an evident either oncogenic or tumor suppressive role in the cancers. In addition, we also focus on the correlation between miRNA deregulation and clinical relevance in cancer patients. On the basis of intriguing findings, the study of miRNAs will provide a new great opportunity to access better clinical management of the malignancies.

Role of microRNAs in the Regulation of Dendritic Cell Generation and Function

Dendritic cells (DCs) are antigen-presenting cells with a key role in immune responses. They act as a link between the innate and adaptive systems and they can induce and maintain immunologic tolerance. DCs are subdivided into conventional and plasmacytoid DCs. These cell subsets originate from the same bone marrow precursors and their differentiation process is determined by several extrinsic and intrinsic factors, such as cytokines, transcription factors, and miRNAs. miRNAs are small non-coding RNAs that play a crucial role in modulating physiological and pathological processes mediated by DCs. miRNA deregulation affects many inflammatory conditions and diseases. The aim of this review was to underline the importance of miRNAs in inflammatory processes mediated by DCs in physiological and pathological conditions and to highlight their potential application for future therapies.