scholarly journals Main N6-Methyladenosine Readers: YTH Family Proteins in Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin-Yuan Dai ◽  
Liang Shi ◽  
Zhi Li ◽  
Hai-Yan Yang ◽  
Ji-Fu Wei ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Rna Splicing ◽  
Mammalian Cells ◽  
Biological Function ◽  
Human Cancer ◽  
Messenger Rnas ◽  
Rna Modifications ◽  
Reversible Process ◽  
Rna Export ◽  
Non Coding Rnas

Among the over 150 RNA modifications, N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNAs, not only in messenger RNAs, but also in microRNAs and long non-coding RNAs. It is a dynamic and reversible process in mammalian cells, which is installed by “writers,” consisting of METTL3, METTL14, WTAP, RBM15/15B, and KIAA1429 and removed by “erasers,” including FTO and ALKBH5. Moreover, m6A modification is recognized by “readers,” which play the key role in executing m6A functions. IYT521-B homology (YTH) family proteins are the first identified m6A reader proteins. They were reported to participate in cancer tumorigenesis and development through regulating the metabolism of targeted RNAs, including RNA splicing, RNA export, translation, and degradation. There are many reviews about function of m6A and its role in various diseases. However, reviews only focusing on m6A readers, especially YTH family proteins are few. In this review, we systematically summarize the recent advances in structure and biological function of YTH family proteins, and their roles in human cancer and potential application in cancer therapy.

scholarly journals Detecting and Characterizing A-to-I MicroRNA Editing in Cancer

2021 ◽  
Author(s):  
Gioacchino P. Marceca ◽  
Luisa Tomasello ◽  
Rosario Distefano ◽  
Mario Acunzo ◽  
Carlo Croce ◽  
...  
Keyword(s):  
Rna Editing ◽  
Rna Splicing ◽  
Cancer Biology ◽  
Human Cancer ◽  
Detection Methods ◽  
Rna Modification ◽  
Messenger Rnas ◽  
Validation Methods ◽  
Non Coding Rnas ◽  
Mirna Editing

RNA editing involves the insertion, deletion or substitution of single nucleotides within a RNA molecule, without altering the DNA sequence. Adenosine to inosine (A-to-I) editing consists of an RNA modification where single adenosines along the RNA sequence are converted into inosines. Such a biochemical transformation is catalyzed by enzymes belonging to the family of adenosine deaminases acting on RNA (ADARs) and occurs either co- or post-transcriptionally. Initially, the A-to-I RNA editing phenomenon was discovered and studied in messenger RNAs (mRNAs), where it can influence RNA splicing and cause the recoding of codon sequences. The employment of more powerful, high-throughput detection methods has recently revealed that A-to-I editing widely occurs in non-coding RNAs, including microRNAs (miRNAs). MiRNAs are a class of small regulatory non-coding RNAs (ncRNAs) acting as translation inhibitors, known to exert relevant roles in controlling cell cycle, proliferation, and cancer development. Indeed, a growing number of recent researches have evidenced the importance of miRNA editing in cancer biology by exploiting various detection and validation methods. Herein, we briefly overview early and currently available A-to-I miRNA editing detection and validation methods and discuss the significance of A-to-I miRNA editing in human cancer.

scholarly journals Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4250
Author(s):  
Xiao-Jing Pang ◽  
Xiu-Juan Liu ◽  
Yuan Liu ◽  
Wen-Bo Liu ◽  
Yin-Ru Li ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Phase I ◽  
Small Molecules ◽  
Anticancer Agents ◽  
Biological Function ◽  
Human Cancer ◽  
Tumor Cell Growth ◽  
Research Groups ◽  
Human Cancer Cell Lines ◽  
Opening Up

FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human cancer cell lines, which promotes tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising cancer therapy with small molecules. Many FAK inhibitors have been reported as anticancer agents with various mechanisms. Currently, six FAK inhibitors, including GSK-2256098 (Phase I), VS-6063 (Phase II), CEP-37440 (Phase I), VS-6062 (Phase I), VS-4718 (Phase I), and BI-853520 (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through “proteolysis targeting chimera” (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new anticancer agents.

scholarly journals CDK12: A Potent Target and Biomarker for Human Cancer Therapy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1483 ◽  
Author(s):  
Shujing Liang ◽  
Lifang Hu ◽  
Zixiang Wu ◽  
Zhihao Chen ◽  
Shuyu Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Therapy ◽  
Gene Transcription ◽  
Rna Splicing ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Human Cancer ◽  
Cellular Processes ◽  
Potential Target ◽  
Human Cancers

Cyclin-dependent kinases (CDKs) are a group of serine/threonine protein kinases and play crucial roles in various cellular processes by regulating cell cycle and gene transcription. Cyclin-dependent kinase 12 (CDK12) is an important transcription-associated CDK. It shows versatile roles in regulating gene transcription, RNA splicing, translation, DNA damage response (DDR), cell cycle progression and cell proliferation. Recently, increasing evidence demonstrates the important role of CDK12 in various human cancers, illustrating it as both a biomarker of cancer and a potential target for cancer therapy. Here, we summarize the current knowledge of CDK12, and review the research advances of CDK12′s biological functions, especially its role in human cancers and as a potential target and biomarker for cancer therapy.

scholarly journals Comprehensive database and evolutionary dynamics of U12-type introns

2020 ◽  
Author(s):  
Devlin C Moyer ◽  
Graham E Larue ◽  
Courtney E Hershberger ◽  
Scott W Roy ◽  
Richard A Padgett
Keyword(s):  
Rna Splicing ◽  
Evolutionary Dynamics ◽  
Messenger Rnas ◽  
Spliceosomal Introns ◽  
Conversion Model ◽  
Nuclear Maturation ◽  
Small Nuclear Ribonucleoprotein ◽  
Associated Proteins ◽  
Non Coding Rnas ◽  
Nuclear Ribonucleoprotein

Abstract During nuclear maturation of most eukaryotic pre-messenger RNAs and long non-coding RNAs, introns are removed through the process of RNA splicing. Different classes of introns are excised by the U2-type or the U12-type spliceosomes, large complexes of small nuclear ribonucleoprotein particles and associated proteins. We created intronIC, a program for assigning intron class to all introns in a given genome, and used it on 24 eukaryotic genomes to create the Intron Annotation and Orthology Database (IAOD). We then used the data in the IAOD to revisit several hypotheses concerning the evolution of the two classes of spliceosomal introns, finding support for the class conversion model explaining the low abundance of U12-type introns in modern genomes.

scholarly journals Updated Database and Evolutionary Dynamics of U12-Type Introns

2019 ◽  
Author(s):  
Devlin C. Moyer ◽  
Graham E. Larue ◽  
Courtney E. Hershberger ◽  
Scott W. Roy ◽  
Richard A. Padgett
Keyword(s):  
Rna Splicing ◽  
Evolutionary Dynamics ◽  
Messenger Rnas ◽  
Spliceosomal Introns ◽  
Conversion Model ◽  
Nuclear Maturation ◽  
Small Nuclear Ribonucleoprotein ◽  
Associated Proteins ◽  
Non Coding Rnas ◽  
Nuclear Ribonucleoprotein

ABSTRACTDuring nuclear maturation of most eukaryotic pre-messenger RNAs and long non-coding RNAs, introns are removed through the process of RNA splicing. Different classes of introns are excised by the U2-type or the U12-type spliceosomes, large complexes of small nuclear ribonucleoprotein particles and associated proteins. We created intronIC, a program for assigning intron class to all introns in a given genome, and used it on 24 eukaryotic genomes to create the Intron Annotation and Orthology Database (IAOD). We then used the data in the IAOD to revisit several hypotheses concerning the evolution of the two classes of spliceosomal introns, finding support for the class conversion model explaining the low abundance of U12-type introns in modern genomes.

scholarly journals LncRNA HOXA-AS2 promotes tumor progression via suppressing miR- 567 expression in Oral Squamous Cell Carcinoma 

2021 ◽  
Author(s):  
Rui Chen ◽  
Xi Wang ◽  
Shixian Zhou ◽  
Zongyue Zeng
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Biological Function ◽  
Human Cancer ◽  
Direct Interaction ◽  
Poor Survival ◽  
Non Coding Rnas

Abstract Growing evidence shows that long non-coding RNAs (lncRNAs), such as lncRNA HOXA-AS2, have emerged as critical regulators in human cancer. However, the biological function and detail regulating mechanisms that how lncRNA HOXA-AS2 played in oral squamous cell carcinoma (OSCC) remains unexplored. In this study, high expression of lncRNA HOXA-AS2 was determined in OSCC cell lines and clinical tissues, which positively correlated with advanced TNM stage and poor survival of OSCC patients. In mechanism, we found that lncRNA HOXA-AS2 negatively regulated miR-567 expression by direct interaction. Additionally, we also found that the expression of miR-567 inversely decreased in OSCC tissues along with the up-regulation of lncRNA HOXA-AS2. Functionally, overexpression of lncRNA HOXA-AS2 significantly promoted OSCC cell proliferation, while knockdown of lncRNA HOXA-AS2 significantly inhibited it. Additionally, we determined that miR-567 targeted to CDK8 directly at the 3’ UTR. In conclusion, lncRNA HOXA-AS2 was up-rugulated in OSCC, correlated with poor clinical outcomes, and promoted OSCC cell proliferation via sponging miR-567 to promote CDK8 expression. Therefore, the potential prognostic value of lncRNA HOXA-AS2 could be explored further.

scholarly journals Functional Interplay between RNA Viruses and Non-Coding RNA in Mammals

2019 ◽  
Vol 5 (1) ◽  
pp. 7 ◽  
Author(s):  
Nkerorema Djodji Damas ◽  
Nicolas Fossat ◽  
Troels K. H. Scheel
Keyword(s):  
Metabolic Pathways ◽  
Mammalian Cells ◽  
Rna Viruses ◽  
Rna Virus ◽  
Messenger Rnas ◽  
Host Interactions ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Antiviral Targets ◽  
Replicative Cycle

Exploring virus–host interactions is key to understand mechanisms regulating the viral replicative cycle and any pathological outcomes associated with infection. Whereas interactions at the protein level are well explored, RNA interactions are less so. Novel sequencing methodologies have helped uncover the importance of RNA–protein and RNA–RNA interactions during infection. In addition to messenger RNAs (mRNAs), mammalian cells express a great number of regulatory non-coding RNAs, some of which are crucial for regulation of the immune system whereas others are utilized by viruses. It is thus becoming increasingly clear that RNA interactions play important roles for both sides in the arms race between virus and host. With the emerging field of RNA therapeutics, such interactions are promising antiviral targets. In this review, we discuss direct and indirect RNA interactions occurring between RNA viruses or retroviruses and host non-coding transcripts upon infection. In addition, we review RNA virus derived non-coding RNAs affecting immunological and metabolic pathways of the host cell typically to provide an advantage to the virus. The relatively few known examples of virus–host RNA interactions suggest that many more await discovery.

DEGRADATION OF MESSENGER RNA IN MAMMALIAN CELLS

1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S369-S380 ◽  
Author(s):  
Francis T. Kenney ◽  
Kai-Lin Lee ◽  
Charles D. Stiles
Keyword(s):  
Messenger Rna ◽  
Mammalian Cells ◽  
Messenger Rnas ◽  
Tyrosine Transaminase

ABSTRACT Analyses of the response of hydrocortisone-induced tyrosine transaminase in cultured H-35 cells to inhibitors of translation (cycloheximide, puromycin) suggest: (1) that bound ribosomes stabilize messenger RNA in vivo; (2) that messenger is degraded at a rate determined by the rate of translation. Since specific messenger RNAs of mammalian cells are degraded at quite different rates, there may be extensive heterogeneity either in the rate at which ribosomes traverse different messengers or in the number of ribosomes which translate specific messenger RNAs.

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