skip to main content


Title: AFAP1‐AS1 : A novel oncogenic long non‐coding RNA in human cancers
Abstract

Long non‐codingRNAs (lncRNAs), a group of non‐protein‐codingRNAs with more than 200 nucleotides in length, are involved in multiple biological processes, such as the proliferation, apoptosis, migration and invasion. Moreover, numerous studies have shown that lncRNAs play important roles as oncogenes or tumour suppressor genes in human cancers. In this paper, we concentrate on actin filament‐associated protein 1‐antisenseRNA1 (AFAP1‐AS1), a well‐known long non‐codingRNAthat is overexpressed in various tumour tissues and cell lines, including oesophageal cancer, pancreatic ductal adenocarcinoma, nasopharyngeal carcinoma, lung cancer, hepatocellular carcinoma, ovarian cancer, colorectal cancer, biliary tract cancer and gastric cancer. Moreover, high expression ofAFAP1‐AS1was associated with the clinicopathological features and cancer progression. In this review, we sum up the current studies on the characteristics ofAFAP1‐AS1in the biological function and mechanism of human cancers.

 
more » « less
NSF-PAR ID:
10045384
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley-Blackwell
Date Published:
Journal Name:
Cell Proliferation
Volume:
51
Issue:
1
ISSN:
0960-7722
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Summary

    The flowering plantArabidopsis thalianais a dicot model organism for research in many aspects of plant biology. A comprehensive annotation of its genome paves the way for understanding the functions and activities of all types of transcripts, includingmRNA, the various classes of non‐codingRNA, and smallRNA. TheTAIR10 annotation update had a profound impact on Arabidopsis research but was released more than 5 years ago. Maintaining the accuracy of the annotation continues to be a prerequisite for future progress. Using an integrative annotation pipeline, we assembled tissue‐specificRNA‐Seq libraries from 113 datasets and constructed 48 359 transcript models of protein‐coding genes in eleven tissues. In addition, we annotated various classes of non‐codingRNAincluding microRNA, long intergenicRNA, small nucleolarRNA, natural antisense transcript, small nuclearRNA, and smallRNAusing published datasets and in‐house analytic results. Altogether, we identified 635 novel protein‐coding genes, 508 novel transcribed regions, 5178 non‐codingRNAs, and 35 846 smallRNAloci that were formerly unannotated. Analysis of the splicing events andRNA‐Seq based expression profiles revealed the landscapes of gene structures, untranslated regions, and splicing activities to be more intricate than previously appreciated. Furthermore, we present 692 uniformly expressed housekeeping genes, 43% of whose human orthologs are also housekeeping genes. This updated Arabidopsis genome annotation with a substantially increased resolution of gene models will not only further our understanding of the biological processes of this plant model but also of other species.

     
    more » « less
  2. Summary

    Plant smallRNAs (sRNAs) modulate key physiological mechanisms through post‐transcriptional and transcriptional silencing of gene expression. SmallRNAs fall into two major categories: those are reliant onRNA‐dependentRNApolymerases (RDRs) for biogenesis and those that are not. KnownRDR1/2/6‐dependentsRNAs include phased and repeat‐associated short interferingRNAs, while knownRDR1/2/6‐independentsRNAs are primarily microRNAs (miRNA) and other hairpin‐derivedsRNAs. In this study we produced and analyzedsRNA‐seq libraries fromrdr1/rdr2/rdr6triple mutant plants. We found 58 previously annotated miRNAloci that were reliant onRDR1, ‐2, or ‐6function, casting doubt on their classification. We also found 38RDR1/2/6‐independentsRNAloci that are notMIRNAs or otherwise hairpin‐derived, and did not fit into other known paradigms forsRNAbiogenesis. These 38sRNA‐producing loci have as‐yet‐undescribed biogenesis mechanisms, and are frequently located in the vicinity of protein‐coding genes. Altogether, our analysis suggests that these 38 loci represent one or more undescribed types ofsRNAinArabidopsis thaliana.

     
    more » « less
  3. Summary

    Here we report the expression of programmed cell death ligand 1/2 (PD‐L1/L2) in breast and colon cancer stem cells (CSCs). The stemness of these cells was confirmed by their surface markers. Using flow cytometry analysis we demonstrated thatPD‐L1 expression was higher inCSCs of both cancers compared to non‐stem like cancer cells. Consistent with this, detection of cellularPD‐L1 proteins by western blot assay also showed increasedPD‐L1 protein inCSCs. In contrast, only trace amounts ofPD‐L2 were detected inCSCs of both cancers. Our results suggest that breast and colon cancers may be sensitive toPD1/PD‐L1 immunotherapy and thus warrant further investigations ofCSCtargetedPD1/PD‐L1 therapy.

     
    more » « less
  4. Summary

    Spirodela polyrhizais a fast‐growing aquatic monocot with highly reduced morphology, genome size and number of protein‐coding genes. Considering these biological features of Spirodela and its basal position in the monocot lineage, understanding its genome architecture could shed light on plant adaptation and genome evolution. Like many draft genomes, however, the 158‐Mb Spirodela genome sequence has not been resolved to chromosomes, and important genome characteristics have not been defined. Here we deployed rapid genome‐wide physical maps combined with high‐coverage short‐read sequencing to resolve the 20 chromosomes of Spirodela and to empirically delineate its genome features. Our data revealed a dramatic reduction in the number of therDNArepeat units in Spirodela to fewer than 100, which is even fewer than that reported for yeast. Consistent with its unique phylogenetic position, smallRNAsequencing revealed 29 Spirodela‐specific microRNA, with only two being shared withElaeis guineensis(oil palm) andMusa balbisiana(banana). CombiningDNAmethylation data and smallRNAsequencing enabled the accurate prediction of 20.5% long terminal repeats (LTRs) that doubled the previous estimate, and revealed a high Solo:IntactLTRratio of 8.2. Interestingly, we found that Spirodela has the lowest globalDNAmethylation levels (9%) of any plant species tested. Taken together our results reveal a genome that has undergone reduction, likely through eliminating non‐essential protein coding genes,rDNAandLTRs. In addition to delineating the genome features of this unique plant, the methodologies described and large‐scale genome resources from this work will enable future evolutionary and functional studies of this basal monocot family.

     
    more » « less
  5. Summary

    In plants, 24 nucleotide long heterochromatic siRNAs (het‐siRNAs) transcriptionally regulate gene expression byRNA‐directedDNAmethylation (RdDM). The biogenesis of most het‐siRNAs depends on the plant‐specificRNApolymeraseIV(PolIV), andARGONAUTE4 (AGO4) is a major het‐siRNAeffector protein. Through genome‐wide analysis ofsRNA‐seq data sets, we found thatAGO4is required for the accumulation of a small subset of het‐siRNAs. The accumulation ofAGO4‐dependent het‐siRNAs also requires several factors known to participate in the effector portion of the RdDMpathway, includingRNA POLYMERASEV (POLV),DOMAINS REARRANGED METHYLTRANSFERASE2 (DRM2) andSAWADEE HOMEODOMAIN HOMOLOGUE1 (SHH1). Like manyAGOproteins,AGO4 is an endonuclease that can ‘slice’RNAs. We found that a slicing‐defectiveAGO4 was unable to fully recoverAGO4‐dependent het‐siRNAaccumulation fromago4mutant plants. Collectively, our data suggest thatAGO4‐dependent siRNAs are secondary siRNAs dependent on the prior activity of the RdDMpathway at certain loci.

     
    more » « less