scholarly journals Therapeutic implications of microRNAs in human cancer

2011 ◽  
Vol 2 (1) ◽  
pp. 3
Author(s):  
Michael Rossbach
Keyword(s):  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Tumor Development ◽  
Gene Profiling ◽  
Protein Coding ◽  
Expression Levels ◽  
Therapeutic Implications ◽  
Novel Drugs ◽  
Antisense Constructs

MicroRNAs (miRNAs) are a class of highly evolutionarily conserved non-coding RNAs (ncRNAs) that modulate gene expression. Several studies have shown that the expression of miRNAs is deregulated in human malignancies. For ncRNAs and miRNAs, such gene-profiling studies in tumorigenic tissues have identified significant signatures that are of both diagnostic and prognostic value. Addressing the functions of ncRNAs not only give insights into the molecular mechanisms that underlie complex genetic processes, but may also elucidate novel mechanisms that contribute to early stages of tumor development, progression and metastasis. MiRNA-based novel approaches target the ncRNAome, including, for instance, miRNA expression levels and improved designs of miRNA-mimics or more precise target-predictions, prevent off-target effects of novel drugs and make miRNAs become a highly efficient class of therapeutics. For miRNA-based therapeutic studies two direct strategies are currently under investigation, viz. (i) the overexpression of given miRNAs to inhibit the expression of protein-coding genes or (ii) the inhibition of target miRNAs with antisense constructs like antagomiRs. Indirect strategies include the use of novel drugs that modulate miRNA expression levels by directly targeting their processing or transcription. Further, miRNA-based biomarkers have a significant impact on the development of both therapeutic and diagnostic agents, a concept known as theranostics and are highly relevant for drug development and personalized medicine.

scholarly journals Small but Heavy Role: MicroRNAs in Hepatocellular Carcinoma Progression

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Erbao Chen ◽  
Xiaojing Xu ◽  
Ruiqi Liu ◽  
Tianshu Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Primary Liver Cancer ◽  
Tumor Development ◽  
Biological Processes ◽  
Regulate Gene Expression ◽  
Small Noncoding Rnas ◽  
Pathological Mechanism ◽  
Cellular Target

Hepatocellular carcinoma (HCC), which accounts for 85–90% of primary liver cancer, is the fifth most common malignant tumor and the third leading cause of cancer-related deaths worldwide, but the pathological mechanism of HCC is still not fully elucidated. miRNAs are evolutionarily endogenous small noncoding RNAs that negatively regulate gene expression via posttranscriptional inhibition or target mRNA degradation in several diseases, especially human cancer. Therefore, discovering the roles of miRNAs is appealing to scientific researchers. Emerging evidence has shown that the aberrant expressions of numerous miRNAs are involved in many HCC biological processes. In hepatocarcinogenesis, miRNAs with dysregulated expression can exert their function as oncogenes or tumor suppressors depending on their cellular target during the cell cycle, and in tumor development, differentiation, apoptosis, angiogenesis, metastasis, and progression of the tumor microenvironment. In this review, we summarize current findings on miRNAs and assess their functions to explore the molecular mechanisms of tumor progression in HCC.

scholarly journals GABRQ is Overexpressed and Correlated with Tumor Progression in Breast Cancer

2021 ◽  
Author(s):  
Ran Mei ◽  
Xichun Cui ◽  
Lili Zheng ◽  
Li Jingyi
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Bioinformatic Analysis ◽  
Gamma Aminobutyric Acid ◽  
Nude Mouse Model ◽  
Expression Levels ◽  
The Public

Abstract Background: Breast cancer (BRCA) is the most common type of women's cancer with a high incidence. The function of gamma-aminobutyric acid A receptor θ subunit (GABRQ) has been studied in other cancers. The results demonstrated that the expression levels of GABRQ were closely associated with tumor prognosis. However, the functions and mechanisms of GABRQ in BRCA remain unclear.Materials and methods: We used the public genome datasets and a tissue microarray (TMA) cohort to analyze the GABRQ expression levels. We performed Immunohistochemistry (IHC) and Western blot to determine GABRQ expression in BRCA cell lines and tissues. Cell proliferation was assessed by EDU assay and colony formation assay. Transwell assay was carried out to investigate the cell invasion ability in vitro and Xenograft nude mouse model was constructed to test the function of GABRQ on tumor growth in vivo. Moreover, we utilized bioinformatic analysis to identify the potential molecular mechanisms mediated by GABRQ modification in BRCA.Results: GABRQ was markedly up-regulated in BRCA tissues, and the expression levels of GABRQ were closely associated with BRCA prognosis. Functional analysis elucidated that knockdown of GABRQ could suppress BRCA cell growth and invasion in vitro, and inhibit tumor development in vivo. Moreover, we found that GABRQ overexpression activated the EMT signaling pathway.Conclusions: These results demonstrated that the function of GABRQ in BRCA progression provided potential prognostic predictors for BRCA patients.

scholarly journals The Interaction Between Long Non-Coding RNAs and Cancer-Associated Fibroblasts in Lung Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Wenqi Ti ◽  
Jianbo Wang ◽  
Yufeng Cheng
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Cancer Associated Fibroblasts ◽  
Protein Coding ◽  
Sequencing Technologies ◽  
Integral Role ◽  
Tumor Growth And Metastasis

Despite great advances in research and treatment, lung cancer is still one of the most leading causes of cancer-related deaths worldwide. Evidence is mounting that dynamic communication network in the tumor microenvironment (TME) play an integral role in tumor initiation and development. Cancer-associated fibroblasts (CAFs), which promote tumor growth and metastasis, are the most important stroma component in the tumor microenvironment. Consequently, in-depth identification of relevant molecular mechanisms and biomarkers related to CAFs will increase understanding of tumor development process, which is of great significance for precise treatment of lung cancer. With the development of sequencing technologies such as microarray and next-generation sequencing, lncRNAs without protein-coding ability have been found to act as communicators between tumor cells and CAFs. LncRNAs participate in the activation of normal fibroblasts (NFs) to CAFs. Moreover, activated CAFs can influence the gene expression and secretion characteristics of cells through lncRNAs, enhancing the malignant biological process in tumor cells. In addition, lncRNA-loaded exosomes are considered to be another important form of crosstalk between tumor cells and CAFs. In this review, we focus on the interaction between tumor cells and CAFs mediated by lncRNAs in the lung cancer microenvironment, and discuss the analysis of biological function and molecular mechanism. Furthermore, it contributes to paving a novel direction for the clinical treatment of lung cancer.

scholarly journals Long Non-Coding RNAs: The Regulatory Mechanisms, Research Strategies, and Future Directions in Cancers

2020 ◽  
Vol 10 ◽  
Author(s):  
Na Gao ◽  
Yueheng Li ◽  
Jing Li ◽  
Zhengfan Gao ◽  
Zhenzhen Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Tumor Development ◽  
Therapeutic Targets ◽  
Regulatory Mechanisms ◽  
Clinical Implementation ◽  
Research Strategies ◽  
Protein Coding ◽  
Functional Studies ◽  
Diagnosis And Prognosis ◽  
Non Coding Rnas

The development and application of whole genome sequencing technology has greatly broadened our horizons on the capabilities of long non-coding RNAs (lncRNAs). LncRNAs are more than 200 nucleotides in length and lack protein-coding potential. Increasing evidence indicates that lncRNAs exert an irreplaceable role in tumor initiation, progression, as well as metastasis, and are novel molecular biomarkers for diagnosis and prognosis of cancer patients. Furthermore, lncRNAs and the pathways they influence might represent promising therapeutic targets for a number of tumors. Here, we discuss the recent advances in understanding of the specific regulatory mechanisms of lncRNAs. We focused on the signal, decoy, guide, and scaffold functions of lncRNAs at the epigenetic, transcription, and post-transcription levels in cancer cells. Additionally, we summarize the research strategies used to investigate the roles of lncRNAs in tumors, including lncRNAs screening, lncRNAs characteristic analyses, functional studies, and molecular mechanisms of lncRNAs. This review will provide a short but comprehensive description of the lncRNA functions in tumor development and progression, thus accelerating the clinical implementation of lncRNAs as tumor biomarkers and therapeutic targets.

scholarly journals Fusion Genes and RNAs in Cancer Development

2021 ◽  
Vol 7 (1) ◽  
pp. 10
Author(s):  
Kenzui Taniue ◽  
Nobuyoshi Akimitsu
Keyword(s):  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Chromosomal Rearrangements ◽  
Tumor Development ◽  
Cancer Development ◽  
Gene Fusions ◽  
Fusion Genes ◽  
Therapeutic Implications ◽  
Downstream Signaling

Fusion RNAs are a hallmark of some cancers. They result either from chromosomal rearrangements or from splicing mechanisms that are non-chromosomal rearrangements. Chromosomal rearrangements that result in gene fusions are particularly prevalent in sarcomas and hematopoietic malignancies; they are also common in solid tumors. The splicing process can also give rise to more complex RNA patterns in cells. Gene fusions frequently affect tyrosine kinases, chromatin regulators, or transcription factors, and can cause constitutive activation, enhancement of downstream signaling, and tumor development, as major drivers of oncogenesis. In addition, some fusion RNAs have been shown to function as noncoding RNAs and to affect cancer progression. Fusion genes and RNAs will therefore become increasingly important as diagnostic and therapeutic targets for cancer development. Here, we discuss the function, biogenesis, detection, clinical relevance, and therapeutic implications of oncogenic fusion genes and RNAs in cancer development. Further understanding the molecular mechanisms that regulate how fusion RNAs form in cancers is critical to the development of therapeutic strategies against tumorigenesis.

scholarly journals 3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 613 ◽  
Author(s):  
Linas Kunigenas ◽  
Vaidotas Stankevicius ◽  
Audrius Dulskas ◽  
Elzbieta Budginaite ◽  
Gediminas Alzbutas ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Lines ◽  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Tumor Tissue ◽  
Differentially Expressed ◽  
Altered Expression ◽  
Expression Levels ◽  
3D Microenvironment ◽  
Long Course

Altered expression of miRNAs in tumor tissue encourages the translation of this specific molecular pattern into clinical practice. However, the establishment of a selective biomarker signature for many tumor types remains an inextricable challenge. For this purpose, a preclinical experimental design, which could maintain a fast and sensitive discovery of potential biomarkers, is in demand. The present study suggests that the approach of 3D cell cultures as a preclinical cancer model that is characterized to mimic a natural tumor environment maintained in solid tumors could successfully be employed for the biomarker discovery and validation. Subsequently, in this study, we investigated an environment-dependent miRNA expression changes in colorectal adenocarcinoma DLD1 and HT29 cell lines using next-generation sequencing (NGS) technology. We detected a subset of 16 miRNAs differentially expressed in both cell lines cultivated in multicellular spheroids compared to expression levels in cells grown in 2D. Furthermore, results of in silico miRNA target analysis showed that miRNAs, which were differentially expressed in both cell lines grown in MCS, are involved in the regulation of molecular mechanisms implicated in cell adhesion, cell-ECM interaction, and gap junction pathways. In addition, integrins and platelet-derived growth factor receptors were determined to be the most significant target genes of deregulated miRNAs, which was concordant with the environment-dependent gene expression changes validated by RT-qPCR. Our results revealed that 3D microenvironment-dependent deregulation of miRNA expression in CRC cells potentially triggers essential molecular mechanisms predominantly including the regulation of cell adhesion, cell–cell, and cell–ECM interactions important in CRC initiation and development. Finally, we demonstrated increased levels of selected miR-142-5p in rectum tumor tissue samples after neoadjuvant long course treatment compared to miR-142-5p expression levels in tumor biopsy samples collected before the therapy. Remarkably, the elevation of miR-142-5p expression remained in tumor samples compared to adjacent normal rectum tissue as well. Therefore, the current study provides valuable insights into the molecular miRNA machinery of CRC and proposes a potential miRNA signature for the assessment of CRC in further clinical research.

Update on MicroRNA-based Treatment Strategies

2021 ◽  
Vol 30 (03) ◽  
pp. 243-250
Author(s):  
Eric Hesse ◽  
Franz Jakob ◽  
Hanna Taipaleenmäki
Keyword(s):  
Treatment Strategies ◽  
Protein Coding ◽  
Therapeutic Implications ◽  
The Public ◽  
Drug Candidates ◽  
Diagnostic Use ◽  
Recent Success ◽  
Novel Approach ◽  
Novel Drugs ◽  
Novel Drug

AbstractThe family of RNAs comprises several members, protein coding mRNAs and a larger group of non-coding RNAs, which include small, approximately 21-25 nucleotides long microRNAs (miRNAs). In addition to an evolving diagnostic use of RNAs, RNA-based drugs are emerging very rapidly in medicine, which is not only -but currently very prominently visible- due to the impressive success of the first-in-class Covid-19 vaccines such as Comirnaty and Moderna (marketed by the companies Biontech/Pfizer and Moderna, respectively). Although administration of RNA-based drugs comes along with several technical obstacles including delivery approaches, the technology is experiencing a breakthrough and technical and conceptual hurdles that may still remain are very likely to be overcome within the near future. It is therefore highly likely that RNA-based pharmacotherapies may revolutionize medicine by improving vaccination concepts but also by providing novel drugs to treat many other conditions like cancer, metabolic- and degenerative diseases and beyond. It is fascinating to witness the rise of such milestones in medicine and is tempting to elaborate which additional accomplishments can be made using this technology towards personalized medicine comprising diagnostic and therapeutic aspects as well as individual drug design.Although the most recent success with mRNA-based and therefore protein coding vaccines currently takes center stage in media and people’s life, other types of RNAs that are less prominent to the public, like non-coding miRNAs, also develop very successfully towards diagnostic and therapeutic purposes. While the diagnostic use of miRNAs was reviewed in another article in this issue (see article from Hackl et al., this issue), this brief review will provide an update on the emerging therapeutic implications of miRNAs. Despite the fact that no miRNA-based drug has yet reached clinical approval, several compounds are in pre-clinical and clinical development for the treatment of various diseases and great progress has been made during the recent years, which also facilitated the establishment of several innovative biotech companies.Several obstacles associated with this novel approach including off-target effects, tissue specificity and delivery systems exist. However, important improvements have already been made and will continue to be made. It can therefore be assumed that treatments using this class of RNA will also further progress and stimulate additional stakeholders to enter the field to develop novel drug candidates as first-in-class medicinal products to address highly unmet clinical needs. This technology is still at its infancy given that miRNAs were uncovered just about 20 years ago but the conditions are promising for the development of next generation miRNA-based drugs.

A Mucin-Specific Protease Enables Molecular and Functional Analysis of Human Cancer-Associated Mucins

2018 ◽  
Author(s):  
Stacy A. Malaker ◽  
Kayvon Pedram ◽  
Michael J. Ferracane ◽  
Elliot C. Woods ◽  
Jessica Kramer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
High Resolution Mass Spectrometry ◽  
Human Cancer ◽  
Glycosylation Sites ◽  
Bacterial Protease ◽  
Specific Protease ◽  
To Come ◽  
And Function

<div> <div> <div> <p>Mucins are a class of highly O-glycosylated proteins that are ubiquitously expressed on cellular surfaces and are important for human health, especially in the context of carcinomas. However, the molecular mechanisms by which aberrant mucin structures lead to tumor progression and immune evasion have been slow to come to light, in part because methods for selective mucin degradation are lacking. Here we employ high resolution mass spectrometry, polymer synthesis, and computational peptide docking to demonstrate that a bacterial protease, called StcE, cleaves mucin domains by recognizing a discrete peptide-, glycan-, and secondary structure- based motif. We exploited StcE’s unique properties to map glycosylation sites and structures of purified and recombinant human mucins by mass spectrometry. As well, we found that StcE will digest cancer-associated mucins from cultured cells and from ovarian cancer patient-derived ascites fluid. Finally, using StcE we discovered that Siglec-7, a glyco-immune checkpoint receptor, specifically binds sialomucins as biological ligands, whereas the related Siglec-9 receptor does not. Mucin-specific proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of glycoprotein structure and function and for deorphanizing mucin-binding receptors. </p> </div> </div> </div>

NOB1: A Potential Biomarker or Target in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 1081-1089
Author(s):  
Weiwei Ke ◽  
Zaiming Lu ◽  
Xiangxuan Zhao
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Binding Protein ◽  
Tumor Development ◽  
Anticancer Therapy ◽  
Research Progress ◽  
Normal Tissues ◽  
Potential Biomarker

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

A Comprehensive Review on Pharmacology and Toxicology of Bioactive Compounds of Lagerstroemia Speciosa (L.) Pers.

2020 ◽  
Vol 06 ◽  
Author(s):  
Surya Kant Tripathi ◽  
Sunayna Behera ◽  
Munmun Panda ◽  
Gokhan Zengin ◽  
Bijesh K. Biswal
Keyword(s):  
Molecular Mechanisms ◽  
Biological Activities ◽  
Health Benefit ◽  
Biologically Active ◽  
Pharmacological Properties ◽  
Lagerstroemia Speciosa ◽  
Novel Drugs ◽  
Corosolic Acid ◽  
Current Article ◽  
Preclinical And Clinical Studies

Background: Lagerstroemia speciosa (L.) Pers is one of the most valuable plants due to its ornamental and pharmacological relevance. It is known for its anti-diabetic activity with proved potent blood sugar-lowering activity. The anti-diabetic activity is due to presence of its biologically active component corosolic acid. Moreover, L. speciosa and its novel purified compounds are also well-known for its several biological activities with beneficial health benefit on the human being. Objectives: This review provides a summary of pharmacokinetics, toxicity, and pharmacological properties of L. speciosa and its purified phytochemicals which may help researchers for building up new researches in near future. Methods: The current article is prepared by collecting through various online and offline databases. Preliminary source of study and data collection for outlining the review was research articles and reviews that have been already published by many reputed publishers, including Springer, Elsevier, Taylor & Francis imprints, BMC, Willy, The Norwegian Academy of Science and Letters, Environmental health prospective (EHP), and PLOS One. Result: The available studies results suggested that the L. speciosa and its phytochemicals showed antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiviral, anti-obesity, and cardio-protective activities. Pharmacokinetic stud-ies suggested the low bioavailability of its purified compounds. However, nano-encapsulation can improve the bioavaila-bility related issue and effectively potentiate the medicinal properties of its constituents. Conclusion: Considering the worthy pharmacological properties, L. speciosa is considered as a potent source of several novel drugs. Though, still preclinical and clinical studies are needed to reveal the targets, molecular mechanisms, bioavail-ability, and toxicity of its constituents.

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