scholarly journals Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Alessandro Allegra ◽  
Manuela Mania ◽  
Angela D’Ascola ◽  
Giacomo Oteri ◽  
Enrico Nastro Siniscalchi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Metabolic Pathways ◽  
Noncoding Rna ◽  
Protective Action ◽  
Noncoding Rnas ◽  
Osteonecrosis Of The Jaw ◽  
Base Pairs ◽  
Osteolytic Lesions ◽  
Ctrl Group ◽  
Rna Molecules

Bisphosphonates (BPs) are inhibitors of osteoclast-mediated bone resorption used for the treatment of multiple myeloma (MM) patients with osteolytic lesions. Bisphosphonate-induced osteonecrosis of the jaw (BONJ) is an infrequent drug-caused adverse event of these agents. Long noncoding RNAs (lncRNAs) are a set of more than 200 base pairs, noncoding RNA molecules, which are critical posttranscriptional regulators of gene expression. Our study was aimed at evaluating 17 lncRNAs, whose targets were previously validated as key elements in MM, bone metabolism, and angiogenesis in MM subjects without BONJ (MM group), in MM subjects with BONJ (BONJ group), and a group of healthy controls (CTRL group). Our results demonstrated a different lncRNA profile in BONJ patients compared to MM patients and controls. Two lncRNAs (DANCR and MALAT1) were both downregulated compared to controls and MM, twelve (HOTAIR, MEG3, TP73-AS1, HOTTIP, HIF1A-AS2, MANTIS, CTD-2201E18, CTD1-2003C8, R-471B22, RP1-43E13, RP11-553L6.5, and RP1-286D6) were overexpressed in MM with BONJ, and one (H19) was upregulated compared with only MM. Two lncRNAs (JHDMD1 and MTMR9LP) had higher expression, but these differences were not statistically significant. The examined lncRNAs target several genes and metabolic pathways. An altered lncRNA signature could contribute to the onset of BONJ or have a protective action. Targeting these lncRNAs could offer a possibility for the prevention or therapy of BONJ.

Tooth Extraction Locally Stimulates Proliferation of Multiple Myeloma in a Patient with Mandibular Localizations

2017 ◽  
Vol 138 (4) ◽  
pp. 201-207 ◽  
Author(s):  
Jean-Daniel Kün-Darbois ◽  
Léonie Quenel ◽  
Smaïl Badja ◽  
Daniel Chappard
Keyword(s):  
Multiple Myeloma ◽  
Tooth Extraction ◽  
Soft Tissues ◽  
Plasma Cells ◽  
Osteonecrosis Of The Jaw ◽  
Surgical Trauma ◽  
Osteolytic Lesions ◽  
X Ray ◽  
Extraction Site ◽  
The Right

Objectives: Multiple myeloma (MM) is characterized by the occurrence of osteolytic lesions. MM treatment usually involves antiresorptive drugs (mainly bisphosphonates). Case Report: A patient with an MM presented osteolytic lesions of the mandible. Extraction of teeth 45 and 46 was performed 5 years after the diagnosis of periodontitis. Four months later, osteonecrosis of the jaw (ONJ) was diagnosed at the extraction site. X-ray showed an extension of osteolytic lesions on the right side, close to the extraction site, without modification of the lesions on the left side. Two months later, a curettage was performed because of a painful bone sequestration. X-ray showed an extension of the osteolytic lesions on the right side. Results: Histological analysis found a vascularized plasmacytoma of the soft tissues around the ONJ. Analysis of the bone showed mixed lesions with osteonecrotic areas and living bone resorbed by active osteoclasts surrounding a plasmacytoma. The surface area of the osteolytic foci has considerably increased only close to the extraction site. Conclusions: Tooth extraction triggered an ONJ associated with bisphosphonate treatment. However, it also seemed to induce a considerable proliferation of plasma cells at the extraction site; we hypothesize that it is due to the increase in bone remodeling related to the surgical trauma.

scholarly journals Characterization of XR_311113.2 as a MicroRNA Sponge for Pre-ovulatory Ovarian Follicles of Goats via Long Noncoding RNA Profile and Bioinformatics Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Hu Tao ◽  
Juan Yang ◽  
Pengpeng Zhang ◽  
Nian Zhang ◽  
Xiaojun Suo ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
Research Field ◽  
Base Pairs ◽  
Boer Goat ◽  
Luciferase Activity Assay ◽  
New Research

Long noncoding RNAs (lncRNAs) were identified recently as a large class of noncoding RNAs (ncRNAs) with a length ≥200 base pairs (bp). The function and mechanism of lncRNAs have been reported in a growing number of species and tissues. In contrast, the regulatory mechanism of lncRNAs in the goat reproductive system has rarely been reported. In the present study, we sequenced and analyzed the lncRNAs using bioinformatics to identify their expression profiles. As a result, 895 lncRNAs were predicted in the pre-ovulatory ovarian follicles of goats. Eighty-eight lncRNAs were differentially expressed in the Macheng black goat when compared with Boer goat. In addition, the lncRNA XR_311113.2 acted as a sponge of chi-miR-424-5p, as assessed via a luciferase activity assay. Taken together, our findings demonstrate that lncRNAs have potential effects in the ovarian follicles of goats and may represent a promising new research field to understand follicular development.

scholarly journals Long noncoding RNA PVT1 is Regulated by Bromodomain Protein BRD4 in Multiple Myeloma and is Associated with Disease Progression

2020 ◽  
Author(s):  
Hiroshi Handa ◽  
Kazuki Honma ◽  
Tsukasa Oda ◽  
Nobuhiko Kobayashi ◽  
Yuko Kuroda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Disease Progression ◽  
Noncoding Rna ◽  
Plasma Cells ◽  
Noncoding Rnas ◽  
Expression Levels ◽  
Positive Correlation ◽  
Cooperative Effects ◽  
Variant Translocation

Abstract: Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), an lncRNA, is located adjacent to MYC, linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis, however, its role and regulation machinery remain uncertain. We examined PVT1/MYC expression through real time PCR in plasma cells purified from 59 MGUS and 140 MM patients. MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, a MYC superenhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p < 0.0001), and showed positive correlation with disease progression (r = 0.394, p < 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, synchronous downregulation of MYC and PVT1 by JQ1, and no effect of MYC inhibitor on PVT1 expression suggest that the expression of these two genes is coregulated by a superenhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.

scholarly journals Focus on Noncoding RNA Regulation of Plant-Microbe Interactions

2016 ◽  
Vol 29 (3) ◽  
pp. 155-155
Author(s):  
John P. Carr ◽  
Steven A. Whitham
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Rna Regulation ◽  
Rna Molecules ◽  
Microbial Origin ◽  
Microbe Interactions ◽  
Satellite Rnas

Investigations in recent years have uncovered important roles for RNA molecules that do not encode proteins (‘noncoding RNAs’) but which, nevertheless, exert powerful effects on gene expression at both transcriptional and posttranscriptional levels. Our late colleague Biao Ding, who died unexpectedly on June 25, 2015, proposed a Focus Issue on the roles in plant-microbe interactions of noncoding RNAs, whether of plant or microbial origin and including small interfering (si)RNAs, microRNAs, phased siRNAs, and long noncoding RNAs, as well as viroids and satellite RNAs. The Editorial Board of MPMI has decided to dedicate this Focus Issue to the memory of Professor Biao Ding, a valued and deeply missed colleague and friend.

scholarly journals Yeast Telomerase RNA Flexibly Scaffolds Protein Subunits: Results and Repercussions

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2750 ◽  
Author(s):  
David C. Zappulla
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Telomerase Rna ◽  
Protein Subunits ◽  
Rna Molecules ◽  
Yeast Telomerase ◽  
Opportune Time ◽  
Rnp Complex ◽  
Functional Features

It is said that “hindsight is 20-20,” so, given the current year, it is an opportune time to review and learn from experiences studying long noncoding RNAs. Investigation of the Saccharomyces cerevisiae telomerase RNA, TLC1, has unveiled striking flexibility in terms of both structural and functional features. Results support the “flexible scaffold” hypothesis for this 1157-nt telomerase RNA. This model describes TLC1 acting as a tether for holoenzyme protein subunits, and it also may apply to a plethora of RNAs beyond telomerase, such as types of lncRNAs. In this short perspective review, I summarize findings from studying the large yeast telomerase ribonucleoprotein (RNP) complex in the hope that this hindsight will sharpen foresight as so many of us seek to mechanistically understand noncoding RNA molecules from vast transcriptomes.

scholarly journals Long Noncoding RNA PVT1 Is Regulated by Bromodomain Protein BRD4 in Multiple Myeloma and Is Associated with Disease Progression

2020 ◽  
Vol 21 (19) ◽  
pp. 7121
Author(s):  
Hiroshi Handa ◽  
Kazuki Honma ◽  
Tsukasa Oda ◽  
Nobuhiko Kobayashi ◽  
Yuko Kuroda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Monoclonal Gammopathy ◽  
Noncoding Rna ◽  
Plasma Cells ◽  
Noncoding Rnas ◽  
Expression Levels ◽  
Cooperative Effects ◽  
Super Enhancer ◽  
Variant Translocation

Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), a lncRNA, is located adjacent to the gene MYC, which has been linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis. However, its role and regulation remain uncertain. We examined PVT1/MYC expression using real-time PCR in plasma cells purified from 59 monoclonal gammopathy of undetermined significance (MGUS) and 140 MM patients. The MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, an MYC super-enhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p < 0.0001) and were positively correlated with disease progression (r = 0.394, p < 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, the synchronous downregulation of MYC and PVT1 by JQ1, and the lack of effect of the MYC inhibitor on PVT1 expression suggest that the expression of these two genes is co-regulated by a super-enhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.

scholarly journals Long Noncoding RNAs in Neurodegenerative Diseases: Pathogenesis and Potential Implications as Clinical Biomarkers

2021 ◽  
Vol 14 ◽  
Author(s):  
Meng Zhang ◽  
Ping He ◽  
Zhigang Bian
Keyword(s):  
Neurodegenerative Diseases ◽  
Noncoding Rna ◽  
Neurological Diseases ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Diagnostic Methods ◽  
Clinical Settings ◽  
Rna Molecules ◽  
Clinical Biomarkers ◽  
Potential Applicability

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), are progressive and ultimately fatal. NDD onset is influenced by several factors including heredity and environmental cues. Long noncoding RNAs (lncRNAs) are a class of noncoding RNA molecules with: (i) lengths greater than 200 nucleotides, (ii) diverse biological functions, and (iii) highly conserved structures. They directly interact with molecules such as proteins and microRNAs and subsequently regulate the expression of their targets at the genetic, transcriptional, and post-transcriptional levels. Emerging studies indicate the important roles of lncRNAs in the progression of neurological diseases including NDDs. Additionally, improvements in detection technologies have enabled quantitative lncRNA detection and application to circulating fluids in clinical settings. Here, we review current research on lncRNAs in animal models and patients with NDDs. We also discuss the potential applicability of circulating lncRNAs as biomarkers in NDD diagnostics and prognostics. In the future, a better understanding of the roles of lncRNAs in NDDs will be essential to exploit these new therapeutic targets and improve noninvasive diagnostic methods for diseases.

scholarly journals Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1170 ◽  
Author(s):  
Barbara Pardini ◽  
Alexandru Anton Sabo ◽  
Giovanni Birolo ◽  
George Adrian Calin
Keyword(s):  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Cancer Biomarkers ◽  
Serum Levels ◽  
Body Fluids ◽  
Circular Rnas ◽  
Liquid Biopsies ◽  
Rna Molecules ◽  
Small Noncoding Rnas ◽  
Dynamic Treatment

The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease. This last aspect has been developed, especially for certain types of cancers, thanks also to the introduction of new concepts such as liquid biopsies and precision medicine. In this context, there is a growing interest in the application of alternative and noninvasive methodologies to search for cancer biomarkers. The new frontiers of the research lead to a search for RNA molecules circulating in body fluids. Searching for biomarkers in extracellular body fluids represents a better option for patients because they are easier to access, less painful, and potentially more economical. Moreover, the possibility for these types of samples to be taken repeatedly, allows a better monitoring of the disease progression or treatment efficacy for a better intervention and dynamic treatment of the patient, which is the fundamental basis of personalized medicine. RNA molecules, freely circulating in body fluids or packed in microvesicles, have all the characteristics of the ideal biomarkers owing to their high stability under storage and handling conditions and being able to be sampled several times for monitoring. Moreover, as demonstrated for many cancers, their plasma/serum levels mirror those in the primary tumor. There are a large variety of RNA species noncoding for proteins that could be used as cancer biomarkers in liquid biopsies. Among them, the most studied are microRNAs, but recently the attention of the researcher has been also directed towards Piwi-interacting RNAs, circular RNAs, and other small noncoding RNAs. Another class of RNA species, the long noncoding RNAs, is larger than microRNAs and represents a very versatile and promising group of molecules which, apart from their use as biomarkers, have also a possible therapeutic role. In this review, we will give an overview of the most common noncoding RNA species detectable in extracellular fluids and will provide an update concerning the situation of the research on these molecules as cancer biomarkers.

scholarly journals The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mohammad Burhan Uddin ◽  
Zhishan Wang ◽  
Chengfeng Yang
Keyword(s):  
Signaling Pathways ◽  
Malignant Transformation ◽  
Noncoding Rna ◽  
Rna Modification ◽  
Oncogenic Signaling ◽  
Aberrant Expression ◽  
Rna Methylation ◽  
Rna Molecules ◽  
M6a Rna Methylation ◽  
Oncogenic Signaling Pathways

AbstractThe m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m6A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m6A modification in the target mRNAs as well as noncoding RNA transcripts. m6A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m6A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m6A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

scholarly journals Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2

Oncogene ◽  
2021 ◽  
Vol 40 (17) ◽  
pp. 3164-3179
Author(s):  
Yang Liu ◽  
Tianchi Tang ◽  
Xiaosheng Yang ◽  
Peng Qin ◽  
Pusen Wang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Noncoding Rna ◽  
Pancreatic Tumor ◽  
Epithelial Mesenchymal Transition ◽  
Noncoding Rnas ◽  
Ductal Adenocarcinoma ◽  
Overall Survival Rate ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.

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