scholarly journals MiR-29a: a potential therapeutic target and promising biomarker in tumors

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Jin-yan Wang ◽  
Qian Zhang ◽  
Dan-dan Wang ◽  
Wei Yan ◽  
Huan-huan Sha ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Therapeutic Target ◽  
Therapeutic Strategy ◽  
Transcriptional Level ◽  
Additional Insight ◽  
Potential Therapeutic Target ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Novel Therapeutic

MiRNAs, small non-coding RNA molecules, were recognized to be associated with the incidence and development of diverse neoplasms. MiRNAs were small non-coding RNAs that could regulate post-transcriptional level by binding to 3′-UTR of target mRNAs. Amongst which, miR-29a was demonstrated that it had significant impact on oncogenicity in various neoplasms through binding to critical genes which enhanced or inhibited the progression of cancers. MiR-29a participated in kinds of physiological and pathological processes, including virus replication, cell proliferation, differentiation, apoptosis, fibrosis, angiogenesis, tumorigenicity, metastasis, drug-resistance, and so on. According to its sufficient sensitivity and specificity, many studies showed that miR-29a might serve as a potential therapeutic target and promising biomarker in various tumors. In this review, we discussed the functions of miR-29a and its potential application in the diagnosis, treatment and stages of carcinoma, which could provide additional insight to develop a novel therapeutic strategy.

scholarly journals Relevance of long non-coding RNAs in tumour biology

2012 ◽  
Vol 153 (38) ◽  
pp. 1494-1501 ◽  
Author(s):  
Zoltán Nagy ◽  
Diána Rita Szabó ◽  
Adrienn Zsippai ◽  
András Falus ◽  
Károly Rácz ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Biology ◽  
Molecular Diagnostics ◽  
Small Rnas ◽  
Molecular Processes ◽  
Major Fraction ◽  
Rna Molecules ◽  
Mediated Effects ◽  
Non Coding Rna ◽  
Non Coding Rnas

The discovery of the biological relevance of non-coding RNA molecules represents one of the most significant advances in contemporary molecular biology. It has turned out that a major fraction of the non-coding part of the genome is transcribed. Beside small RNAs (including microRNAs) more and more data are disclosed concerning long non-coding RNAs of 200 nucleotides to 100 kb length that are implicated in the regulation of several basic molecular processes (cell proliferation, chromatin functioning, microRNA-mediated effects, etc.). Some of these long non-coding RNAs have been associated with human tumours, including H19, HOTAIR, MALAT1, etc., the different expression of which has been noted in various neoplasms relative to healthy tissues. Long non-coding RNAs may represent novel markers of molecular diagnostics and they might even turn out to be targets of therapeutic intervention. Orv. Hetil., 2012, 153, 1494–1501.

scholarly journals Long non-coding RNA (lncRNA): A potential therapeutic target in acute lung injury

2021 ◽  
Author(s):  
Almaz Zaki ◽  
M Shadab Ali ◽  
Vijay Hadda ◽  
Syed Mansoor Ali ◽  
Anita Chopra ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Rowaida Mohammed Reda M. M Aboushahba ◽  
Fayda Ibrahim Abdel Motaleb ◽  
Ahmed Abdel Aziz Abou-Zeid ◽  
Enas Samir Nabil ◽  
Dalia Abdel-Wahab Mohamed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P < 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

ADAMTS9-AS2: A functional long non-coding RNA in tumorigenesis

2021 ◽  
Vol 27 ◽  
Author(s):  
Wen Xu ◽  
Bei Wang ◽  
Yuxuan Cai ◽  
Jinlan Chen ◽  
Xing Lv ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathways ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Migration Inhibition ◽  
Cancer Proliferation ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Background: Long non-coding RNAs (lncRNA) have been identified as novel molecular regulators in cancers. LncRNA ADAMTS9-AS2 can mediate the occurrence and development of cancer through various ways such as regulating miRNAs, activating the classical signaling pathways in cancer, and so on, which have been studied by many scholars. In this review, we summarize the molecular mechanisms of ADAMTS9-AS2 in different human cancers. Methods: Through a systematic search of PubMed, lncRNA ADAMTS9-AS2 mediated molecular mechanisms in cancer are summarized inductively. Results: ADAMTS9-AS2 aberrantly expression in different cancers is closely related to cancer proliferation, invasion, migration, inhibition of apoptosis. The involvement of ADAMTS9-AS2 in DNA methylation, mediating PI3K / Akt / mTOR signaling pathways, regulating miRNAs and proteins, and such shows its significant potential as a therapeutic cancer target. Conclusion: LncRNA ADAMTS9-AS2 can become a promising biomolecular marker and a therapeutic target for human cancer.

scholarly journals Long-non Coding RNAs Related to Fat Deposition in Pigs Included lncRNA Corresponding to Human MALAT1

2021 ◽  
Author(s):  
Katarzyna Piórkowska ◽  
Kacper Żukowski ◽  
Katarzyna Ropka-Molik ◽  
Mirosław Tyra
Keyword(s):  
Regulatory Elements ◽  
Fat Deposition ◽  
Differentially Expressed ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Sequencing Method ◽  
Non Coding Rnas ◽  
Potential Interactions ◽  
Long Non Coding Rna ◽  
Generation Sequencing

Obesity is a problem in the last decades since the development of different technologies forced the submission of a faster pace of life, resulting in nutrition style changes. In turn, domestic pigs are an excellent animal model in recognition of adiposity-related processes, corresponding to the size of individual organs, the distribution of body fat in the organism, and similar metabolism. The present study applied the next-generation sequencing method to identify adipose tissue (AT) transcriptomic signals related to increased fat content by identifying differentially expressed genes (DEGs), included long-non coding RNA molecules. The Freiburg RNA tool was applied to recognise predicting hybridisation energy of RNA-RNA interactions. The results indicated several long non-coding RNAs (lncRNAs) whose expression was significantly positively or negatively associated with fat deposition. lncRNAs play an essential role in regulating gene expression by sponging miRNA, binding transcripts, facilitating translation, or coding other smaller RNA regulatory elements. In the pig fat tissue of obese group, increased expression of lncRNAs corresponding to human MALAT1 was observed that previously recognised in the obesity-related context. Moreover, hybridisation energy analyses pinpointed numerous potential interactions between identified differentially expressed lncRNAs, and obesity-related genes and miRNAs expressed in AT.

scholarly journals The SARS-CoV-2 conserved macrodomain is a mono-ADP-ribosylhydrolase

2020 ◽  
Author(s):  
Yousef M.O. Alhammad ◽  
Maithri M. Kashipathy ◽  
Anuradha Roy ◽  
Jean-Philippe Gagné ◽  
Peter McDonald ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Therapeutic Target ◽  
Viral Infections ◽  
Protein Domain ◽  
Structural Protein ◽  
Potential Therapeutic Target ◽  
Novel Therapeutic Strategies ◽  
Design And Testing ◽  
Translational Process ◽  
Novel Therapeutic

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-like-CoVs encode 3 tandem macrodomains within non-structural protein 3 (nsp3). The first macrodomain, Mac1, is conserved throughout CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. Mac1 likely counters host-mediated anti-viral ADP-ribosylation, a posttranslational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Here we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose. SARS-CoV-2, SARS-CoV and MERS-CoV Mac1 exhibit similar structural folds and all 3 proteins bound to ADP-ribose with low μM affinities. Importantly, using ADP-ribose detecting binding reagents in both a gel-based assay and novel ELISA assays, we demonstrated de-MARylating activity for all 3 CoV Mac1 proteins, with the SARS-CoV-2 Mac1 protein leading to a more rapid loss of substrate compared to the others. In addition, none of these enzymes could hydrolyze poly-ADP-ribose. We conclude that the SARS-CoV-2 and other CoV Mac1 proteins are MAR-hydrolases with similar functions, indicating that compounds targeting CoV Mac1 proteins may have broad anti-CoV activity.IMPORTANCESARS-CoV-2 has recently emerged into the human population and has led to a worldwide pandemic of COVID-19 that has caused greater than 900 thousand deaths worldwide. With, no currently approved treatments, novel therapeutic strategies are desperately needed. All coronaviruses encode for a highly conserved macrodomain (Mac1) that binds to and removes ADP-ribose adducts from proteins in a dynamic post-translational process increasingly recognized as an important factor that regulates viral infection. The macrodomain is essential for CoV pathogenesis and may be a novel therapeutic target. Thus, understanding its biochemistry and enzyme activity are critical first steps for these efforts. Here we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose, and describe its ADP-ribose binding and hydrolysis activities in direct comparison to SARS-CoV and MERS-CoV Mac1 proteins. These results are an important first step for the design and testing of potential therapies targeting this unique protein domain.

scholarly journals Emerging Roles of Estrogen-Regulated Enhancer and Long Non-Coding RNAs

2020 ◽  
Vol 21 (10) ◽  
pp. 3711
Author(s):  
Melina J. Sedano ◽  
Alana L. Harrison ◽  
Mina Zilaie ◽  
Chandrima Das ◽  
Ramesh Choudhari ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Expression Patterns ◽  
Biological Significance ◽  
Rna Seq ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Non Coding Rnas

Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be “junk” DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.

scholarly journals Long Non-Coding RNAs in Multiple Myeloma

2019 ◽  
Vol 5 (1) ◽  
pp. 13 ◽  
Author(s):  
Romana Butova ◽  
Petra Vychytilova-Faltejskova ◽  
Adela Souckova ◽  
Sabina Sevcikova ◽  
Roman Hajek
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Current Knowledge ◽  
Biological Processes ◽  
Cell Distribution ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
New Treatment ◽  
Long Non Coding Rna

Multiple myeloma (MM) is the second most common hematooncological disease of malignant plasma cells in the bone marrow. While new treatment brought unprecedented increase of survival of patients, MM pathogenesis is yet to be clarified. Increasing evidence of expression of long non-coding RNA molecules (lncRNA) linked to development and progression of many tumors suggested their important role in tumorigenesis. To date, over 15,000 lncRNA molecules characterized by diversity of function and specificity of cell distribution were identified in the human genome. Due to their involvement in proliferation, apoptosis, metabolism, and differentiation, they have a key role in the biological processes and pathogenesis of many diseases, including MM. This review summarizes current knowledge of non-coding RNAs (ncRNA), especially lncRNAs, and their role in MM pathogenesis. Undeniable involvement of lncRNAs in MM development suggests their potential as biomarkers.

Role of GADD45α as a potential therapeutic target for prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10566-10566
Author(s):  
R. Singal ◽  
K. Ramachandran ◽  
G. Gopisetty ◽  
L. Navarro ◽  
E. Gordian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Recombinant Expression ◽  
Proximal Promoter ◽  
Lncap Cells ◽  
Potential Therapeutic Target ◽  
Du145 Cells ◽  
Docetaxel Chemotherapy

10566 Background: Defects in the apoptotic pathway contribute to uncontrolled cell proliferation of cancer cells and confer resistance to chemotherapeutic drugs. Understanding the mechanisms of deregulation of apoptosis related genes would enable targeted treatment methods to improve the efficacy of chemotherapy. Growth Arrest and DNA Damage inducible, alpha (GADD45a) mediates cytotoxicity of docetaxel chemotherapy. We examined the mechanism of regulation of GADD45a in prostate cancer cells and the effect of its upregulation on sensitivity to docetaxel chemotherapy. Methods: Levels of GADD45a in Du145, LNCaP and PC3 were analyzed by real time reverse transcriptase PCR and western blotting. DNA methylation was studied by bisulfite sequencing. Chromatin immunoprecipitation was used to study interaction of methyl binding proteins to GADD45 5’ sequence. Cytotoxicity after drug treatment was measured by MTT cell proliferation assay. Apoptosis assays were done by Annexin V/propidium iodide staining followed by flow cytometry. Results: Levels of expression of GADD45a in Du145 and LNCaP cells were lower than that in PC3. A 4 CpG region upstream of the proximal promoter region was methylated in Du145 and LNCaP cells. Methylation was reversed by treatment of Du145 and LNCaP cells with DNA methyl transferase (DNMT) inhibitors such as 5- Azacytidine or 5- Aza deoxycytidine leading to reactivation of GADD45a expression in these cells. This region was also frequently methylated in prostate cancer tissues. Methyl binding protein, MeCP2 was associated with the methylated 4 CpGs in Du145 and knock down of MeCP2 by transfection of MeCP2 siRNA vector in Du145 cells (Du145-MeCP2-ve) led to increased expression of GADD45a, without affecting the methylation status of the gene. Enhanced sensitivity to docetaxel was observed by upregulation of GADD45a in Du145 cells by (a) recombinant expression of GADD45a (b) downregulation of MeCP2 and (c) pretreatment with 5-Azacytidine. Conclusions: GADD45a is frequently deregulated in prostate cancer by methylation of 5’ 4 CpG region and is a potential therapeutic target for treatment of prostate cancer. [Table: see text]

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