Loss of RBMS1 as a regulatory target of miR-106b influences cell growth, gap closing and colony forming in prostate carcinoma

Abstract Prostate carcinoma (PCa) is the second most commonly diagnosed cancer in males worldwide. Among hereditary genetic mutations and nutrient factors, a link between the deregulation of microRNA (miRNA) expression and the development of prostate carcinoma is assumed. MiRNAs are small non-coding RNAs which post-transcriptionally regulate gene expression and which are involved in tumour development and progression as oncogenes or tumour suppressors. Although many genes could be confirmed as targets for deregulated miRNAs, the impact of differentially expressed miRNA and their regulatory target genes on prostate tumour development and progression are not fully understood yet. We could validate RBMS1, a barely described RNA-binding protein, as a new target gene for oncogenic miR-106b, which was identified as an induced miRNA in PCa. Further analysis revealed a loss of RBMS1 expression in prostate tumours compared to corresponding normal tissue. Overexpression of RBMS1 in DU145 and LNCaP prostate cancer cells resulted in diminished cell proliferation, colony forming ability as well as in retarded gap closing. Our results demonstrate for the first time a miR-106b dependent downregulation of RBMS1 in prostate carcinoma. Additionally, we show new tumour suppressive properties of RBMS1 whose observed loss may further elucidate the development of PCa.

Download Full-text

MicroRNAs: role in cardiovascular biology and disease

Clinical Science ◽

10.1042/cs20070211 ◽

2008 ◽

Vol 114 (12) ◽

pp. 699-706 ◽

Cited By ~ 78

Author(s):

Chunxiang Zhang

Keyword(s):

Cardiovascular Diseases ◽

Target Genes ◽

Future Research ◽

Cardiovascular Development ◽

Biological Functions ◽

Lesion Formation ◽

Regulate Gene Expression ◽

Proliferation And Apoptosis ◽

Cardiovascular Biology ◽

Non Coding Rnas

miRNAs (microRNAs) comprise a novel class of endogenous, small, non-coding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Recent studies have demonstrated that miRNAs are highly expressed in the cardiovascular system. Although we are currently in the initial stages of understanding how this novel class of gene regulators is involved in cardiovascular biological functions, a growing body of exciting evidence suggests that miRNAs are important regulators of cardiovascular cell differentiation, growth, proliferation and apoptosis. Moreover, miRNAs are key modulators of both cardiovascular development and angiogenesis. Consequently, dysregulation of miRNA function may lead to cardiovascular diseases. Indeed, several recent reports have demonstrated that miRNAs are aberrantly expressed in diseased hearts and vessels. Modulating these aberrantly expressed miRNAs has significant effects on cardiac hypertrophy, vascular neointimal lesion formation and cardiac arrhythmias. Identifying the roles of miRNAs and their target genes and signalling pathways in cardiovascular disease will be critical for future research. miRNAs may represent a new layer of regulators for cardiovascular biology and a novel class of therapeutic targets for cardiovascular diseases.

Download Full-text

The PARP Inhibitor Olaparib Modulates the Transcriptional Regulatory Networks of Long Non-Coding RNAs during Vasculogenic Mimicry

Cells ◽

10.3390/cells9122690 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2690

Author(s):

Mónica Fernández-Cortés ◽

Eduardo Andrés-León ◽

Francisco Javier Oliver

Keyword(s):

Transcription Factors ◽

Binding Sites ◽

Regulatory Networks ◽

Target Genes ◽

Parp Inhibitor ◽

Vasculogenic Mimicry ◽

Transcriptome Profiling ◽

Key Species ◽

Non Coding Rnas ◽

The Impact

In highly metastatic tumors, vasculogenic mimicry (VM) involves the acquisition by tumor cells of endothelial-like traits. Poly-(ADP-ribose) polymerase (PARP) inhibitors are currently used against tumors displaying BRCA1/2-dependent deficient homologous recombination, and they may have antimetastatic activity. Long non-coding RNAs (lncRNAs) are emerging as key species-specific regulators of cellular and disease processes. To evaluate the impact of olaparib treatment in the context of non-coding RNA, we have analyzed the expression of lncRNA after performing unbiased whole-transcriptome profiling of human uveal melanoma cells cultured to form VM. RNAseq revealed that the non-coding transcriptomic landscape differed between olaparib-treated and non-treated cells: olaparib significantly modulated the expression of 20 lncRNAs, 11 lncRNAs being upregulated, and 9 downregulated. We subjected the data to different bioinformatics tools and analysis in public databases. We found that copy-number variation alterations in some olaparib-modulated lncRNAs had a statistically significant correlation with alterations in some key tumor suppressor genes. Furthermore, the lncRNAs that were modulated by olaparib appeared to be regulated by common transcription factors: ETS1 had high-score binding sites in the promoters of all olaparib upregulated lncRNAs, while MZF1, RHOXF1 and NR2C2 had high-score binding sites in the promoters of all olaparib downregulated lncRNAs. Finally, we predicted that olaparib-modulated lncRNAs could further regulate several transcription factors and their subsequent target genes in melanoma, suggesting that olaparib may trigger a major shift in gene expression mediated by the regulation lncRNA. Globally, olaparib changed the lncRNA expression landscape during VM affecting angiogenesis-related genes.

Download Full-text

Manifestly Altered MicroRNAs in Poly Cystic Ovary Syndrome

International Electronic Journal of Medicine ◽

10.34172/iejm.2020.15 ◽

2020 ◽

Vol 9 (2) ◽

pp. 86-91

Author(s):

Mahta Moraghebi ◽

Milad Rafat ◽

Pegah Mousavi ◽

Kianoosh Malekzadeh

Keyword(s):

Target Genes ◽

Large Family ◽

Mirna Expression Profile ◽

Total Blood ◽

Regulate Gene Expression ◽

New Approach ◽

Comprehensive Information ◽

Non Coding Rnas ◽

Ovarian Syndrome

MicroRNAs (miRNAs) constitute a large family of small non-coding RNAs which regulate gene expression at the surface following transcription. They are widely involved in many physiological and pathological processes including polycystic ovarian syndrome (PCOS). PCOS is an endocrine disorder in women. Currently, there is no comprehensive information about the role of miRNAs in PCOS. Thus, this paper has attempted to collate studies on miRNAs in order to determine important changes in their miRNA expression profile in the total blood, serum, plasma, follicular fluid, and granulosa cells in PCOS patients alongside the genes which are targeted for regulation by these miRNAs. This study presents a new approach for using miRNAs and their target genes for diagnosing and treating PCOS.

Download Full-text

MicroRNA-202 Induces Myoblast to Myocyte Differentiation through Targeting Rock-1

10.20944/preprints202112.0343.v1 ◽

2021 ◽

Author(s):

Maryam Honardoost ◽

Mahsa Bourbour ◽

Ehsan Arefian

Keyword(s):

Target Genes ◽

Horse Serum ◽

Expression Patterns ◽

C2c12 Cell ◽

Inhibitory Effect ◽

Luciferase Assay ◽

Differentiation Process ◽

Myocyte Differentiation ◽

Non Coding Rnas ◽

The Impact

Abstract The expression patterns of microRNAs (small non-coding RNAs) are altered in many biological processes such as myogenesis. In this study, we aimed to investigate the impact of predicted miR-202, its target genes Akt2 and Rock-1 as a potential regulator of myoblast in the myocyte differentiation process using the C2C12 cell line. After confirmation of the differentiation process induced by 3% horse serum, the expression level of miRNA and its targets were evaluated. In the following, a luciferase assay was conducted to approve the effect of miRNA on its target. Our results indicated that miR-202 and Akt2 were significantly up-regulated during differentiation, while Rock-1 was downregulated. Co-transfection of miRNA with psiCHECK2-Rock-1 significantly presented that Rock-1 was directly targeted by miR-202. On the contrary, miR-202 has failed to enforce its inhibitory effect on Akt2 expression. In particular, miR-202 seems to be a regulator of muscle differentiation pathway thought targeting Rock-1.

Download Full-text

Interaction Between LncRNA and UPF1 in Tumors

Frontiers in Genetics ◽

10.3389/fgene.2021.624905 ◽

2021 ◽

Vol 12 ◽

Author(s):

Junjian He ◽

Xiaoxin Ma

Keyword(s):

Gene Expression ◽

Rna Binding ◽

Cell Transformation ◽

Rna Binding Protein ◽

Rna Decay ◽

Regulate Gene Expression ◽

Rna Molecules ◽

Key Factor ◽

Non Coding Rnas ◽

Regulate Gene

Long non-coding RNAs (LncRNAs) can bind to other proteins or RNAs to regulate gene expression, and its role in tumors has been extensively studied. A common RNA binding protein, UPF1, is also a key factor in a variety of RNA decay pathways. RNA decay pathways serve to control levels of particular RNA molecules. The expression of UPF1 is often dysregulated in tumors, an observation which suggests that UPF1 contributes to development of a variety of tumors. Herein, we review evidence from studies of fourteen lncRNAs interact with UPF1. The interaction between lncRNA and UPFI provide fundamental basis for cell transformation and tumorigenic growth.

Download Full-text

Cancer-Associated circRNA–miRNA–mRNA Regulatory Networks: A Meta-Analysis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.671309 ◽

2021 ◽

Vol 8 ◽

Author(s):

Shaheerah Khan ◽

Atimukta Jha ◽

Amaresh C. Panda ◽

Anshuman Dixit

Keyword(s):

Regulatory Networks ◽

Target Genes ◽

Rna Binding ◽

Meta Analysis ◽

Study Data ◽

Circular Rnas ◽

Rna Molecules ◽

Sequencing Technologies ◽

Non Coding Rnas

Recent advances in sequencing technologies and the discovery of non-coding RNAs (ncRNAs) have provided new insights in the molecular pathogenesis of cancers. Several studies have implicated the role of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and recently discovered circular RNAs (circRNAs) in tumorigenesis and metastasis. Unlike linear RNAs, circRNAs are highly stable and closed-loop RNA molecules. It has been established that circRNAs regulate gene expression by controlling the functions of miRNAs and RNA-binding protein (RBP) or by translating into proteins. The circRNA–miRNA–mRNA regulatory axis is associated with human diseases, such as cancers, Alzheimer’s disease, and diabetes. In this study, we explored the interaction among circRNAs, miRNAs, and their target genes in various cancers using state-of-the-art bioinformatics tools. We identified differentially expressed circRNAs, miRNAs, and mRNAs on multiple cancers from publicly available data. Furthermore, we identified many crucial drivers and tumor suppressor genes in the circRNA–miRNA–mRNA regulatory axis in various cancers. Together, this study data provide a deeper understanding of the circRNA–miRNA–mRNA regulatory mechanisms in cancers.

Download Full-text

RBPSponge: genome-wide identification of lncRNAs that sponge RBPs

Bioinformatics ◽

10.1093/bioinformatics/btz448 ◽

2019 ◽

Vol 35 (22) ◽

pp. 4760-4763 ◽

Cited By ~ 7

Author(s):

Saber HafezQorani ◽

Aissa Houdjedj ◽

Mehmet Arici ◽

Abdesselam Said ◽

Hilal Kazan

Keyword(s):

Binding Sites ◽

Regulatory Network ◽

Target Genes ◽

Rna Binding ◽

Rna Binding Protein ◽

Supplementary Information ◽

Web Tool ◽

Genome Wide ◽

Non Coding Rnas ◽

The Web

Abstract Summary Long non-coding RNAs (lncRNAs) can act as molecular sponge or decoys for an RNA-binding protein (RBP) through their RBP-binding sites, thereby modulating the expression of all target genes of the corresponding RBP of interest. Here, we present a web tool named RBPSponge to explore lncRNAs based on their potential to act as a sponge for an RBP of interest. RBPSponge identifies the occurrences of RBP-binding sites and CLIP peaks on lncRNAs, and enables users to run statistical analyses to investigate the regulatory network between lncRNAs, RBPs and targets of RBPs. Availability and implementation The web server is available at https://www.RBPSponge.com. Supplementary information Supplementary data are available at Bioinformatics online.

Download Full-text

Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study

Cancers ◽

10.3390/cancers12102979 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2979

Author(s):

Antonio Fernandez-Serra ◽

David S. Moura ◽

María Dolores Sanchez-Izquierdo ◽

Silvia Calabuig-Fariñas ◽

Maria Lopez-Alvarez ◽

...

Keyword(s):

High Risk ◽

Target Genes ◽

Prognostic Biomarkers ◽

Transcriptional Level ◽

Prognostic Impact ◽

Relapse Free Survival ◽

Regulate Gene Expression ◽

Free Survival ◽

Qrt Pcr ◽

Non Coding Rnas

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, and they have been described as being associated with tumor prognosis. Here, miRNA profiling was planned to explore new molecular prognostic biomarkers in localized intestinal high-risk GIST. Paraffin tumor blocks of 14 and 86 patients were used in the discovery and expansion sets, respectively. GeneChip miRNA v3.0 was employed to identify the miRNAs differentially expressed between relapsed and non-relapsed patient samples, which were validated in the expansion set, by qRT-PCR. RT2 Profiler PCR Array was used for the screening of let-7e targets. Expression levels were correlated with relapse-free survival and overall survival. In the discovery set, 39 miRNAs were significantly deregulated, let-7e and miR-550 being the most underexpressed and overexpressed miRNAs in the relapsed group, respectively. In the expansion set, the underexpression of let-7e or the overexpression of 4 of its target genes (ACVR1B, CASP3, COL3A1, and COL5A2) were statistically associated with worse relapse-free survival. The expression of let-7e and 4 of its target genes are potential prognostic biomarkers in high-risk localized intestinal GIST. The expression of these genes is a potential molecular tool useful for a more accurate prognosis in this subset of GIST patients.

Download Full-text

The Impact of lncRNAs in Diabetes Mellitus: A Systematic Review and In Silico Analyses

Frontiers in Endocrinology ◽

10.3389/fendo.2021.602597 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cristine Dieter ◽

Natália Emerim Lemos ◽

Nathalia Rodrigues de Faria Corrêa ◽

Taís Silveira Assmann ◽

Daisy Crispim

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Systematic Review ◽

Target Genes ◽

Gene Expression Omnibus ◽

Bioinformatics Analyses ◽

Regulate Gene Expression ◽

The Subject ◽

The Impact ◽

In Silico Analyses

Long non-coding RNAs (lncRNAs) are non-coding transcripts that have emerged as one of the largest and diverse RNA families that regulate gene expression. Accumulating evidence has suggested a number of lncRNAs are involved in diabetes mellitus (DM) pathogenesis. However, results about lncRNA expressions in DM patients are still inconclusive. Thus, we performed a systematic review of the literature on the subject followed by bioinformatics analyses to better understand which lncRNAs are dysregulated in DM and in which pathways they act. Pubmed, Embase, and Gene Expression Omnibus (GEO) repositories were searched to identify studies that investigated lncRNA expression in cases with DM and non-diabetic controls. LncRNAs consistently dysregulated in DM patients were submitted to bioinformatics analysis to retrieve their target genes and identify potentially affected signaling pathways under their regulation. Fifty-three eligible articles were included in this review after the application of the inclusion and exclusion criteria. Six hundred and thirty-eight lncRNAs were differentially expressed between cases and controls in at least one study. Among them, six lncRNAs were consistently dysregulated in patients with DM (Anril, Hotair, Malat1, Miat, Kcnq1ot1, and Meg3) compared to controls. Moreover, these six lncRNAs participate in several metabolism-related pathways, evidencing their importance in DM. This systematic review suggests six lncRNAs are dysregulated in DM, constituting potential biomarkers of this disease.

Download Full-text

MicroRNAs and their role in hematological malignant diseases

Orvosi Hetilap ◽

10.1556/oh.2012.29511 ◽

2012 ◽

Vol 153 (52) ◽

pp. 2051-2059 ◽

Cited By ~ 8

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.

Download Full-text