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Transcriptional analysis of nitrogen fixation in Paenibacillus durus during growth in nitrogen-enriched medium

Halim MA, Choo QC, Ghazali AHA, Wajidi MFF, Najimudin N

Lett Appl Microbiol, 2021 May;72(5):610-618.
PMID: 33525052 DOI: 10.1111/lam.13455

Paenibacillus durus strain ATCC 35681T is a Gram-positive diazotroph that displayed capability of fixing nitrogen even in the presence of nitrate or ammonium. However, the nitrogen fixation activity was detected only at day 1 of growth when cultured in liquid nitrogen-enriched medium. The transcripts of all the nifH homologues were present throughout the 9-day study. When grown in nitrogen-depleted medium, nitrogenase activities occurred from day 1 until day 6 and the nifH transcripts were also present during the course of the study albeit at different levels. In both studies, the absence of nitrogen fixation activity regardless of the presence of the nifH transcripts raised the possibility of a post-transcriptional or post-translational regulation of the system. A putative SigA box sequence was found upstream of the transcription start site of nifB1, the first gene in the major nitrogen fixation cluster. The upstream region of nifB2 showed a promoter recognizable by SigE, a sigma factor normally involved in sporulation.

Matched MeSH terms: Bacterial Proteins/genetics; Nitrogen Fixation/genetics*; Oxidoreductases/genetics*; Promoter Regions, Genetic/genetics; Sigma Factor/genetics; Transcription, Genetic/genetics*; Paenibacillus/genetics*
Contribution of TIMP4 rs3755724 polymorphism to susceptibility to focal epilepsy in Malaysian Chinese

Haerian BS, Sha'ari HM, Fong CY, Tan HJ, Wong SW, Ong LC, et al.

J Neuroimmunol, 2015 Jan 15;278:137-43.
PMID: 25595263 DOI: 10.1016/j.jneuroim.2014.12.016

Neuroinflammation can damage the brain and plays a critical role in the pathophysiology of epilepsy. Tissue inhibitor of metalloproteinase 4 (TIMP4) is an inflammation-induced apoptosis and matrix turnover factor involved in several neuronal disorders and inflammatory diseases. Evidence has shown linkage disequilibrium between rs3755724 (-55C/T) of this gene with synapsin 2 (SYN2) rs3773364 and peroxisome proliferator-activated G receptor (PPARG) rs2920502 loci, which contribute to epilepsy in Caucasians. The aim of this study was to examine the association of these loci alone or their haplotypes with the risk of epilepsy in the Malaysian population. Genomic DNA of 1241 Malaysian Chinese, Indian, and Malay subjects (670 patients with epilepsy and 571 healthy individuals) was genotyped for the candidate loci by using the Sequenom MassArray method. Allele and genotype association of rs3755724 with susceptibility to epilepsy was significant in the Malaysian Chinese with focal epilepsy under codominant and dominant models (C vs. T: 1.5 (1.1-2.0), p=0.02; CT vs. TT: 1.8 (1.2-2.8), p=0.007 and 1.8 (1.2-2.7), p=0.006, respectively). The T allele and the TT genotype were more common in patients than in controls. No significant association was found between rs2920502 and rs3773364-rs3755724-rs2920502 haplotypes for susceptibility to epilepsy in each ethnicity. This study provides evidence that the promoter TIMP4 rs3755724 is a new focal epilepsy susceptibility variant that is plausibly involved in inflammation-induced seizures in Malaysian Chinese.

Matched MeSH terms: Epilepsies, Partial/genetics*; Synapsins/genetics; Tissue Inhibitor of Metalloproteinases/genetics*; Genetic Predisposition to Disease/genetics*; Polymorphism, Single Nucleotide/genetics*; Asian Continental Ancestry Group/genetics; PPAR gamma/genetics
Rapid shifts in methanotrophic bacterial communities mitigate methane emissions from a tropical hydropower reservoir and its downstream river

Reis PCJ, Ruiz-González C, Crevecoeur S, Soued C, Prairie YT

Sci Total Environ, 2020 Dec 15;748:141374.
PMID: 32823225 DOI: 10.1016/j.scitotenv.2020.141374

Methane-oxidizing bacteria (MOB) present in the water column mitigate methane (CH4) emissions from hydropower complexes to the atmosphere. By creating a discontinuity in rivers, dams cause large environmental variations, including in CH4 and oxygen concentrations, between upstream, reservoir, and downstream segments. Although highest freshwater methanotrophic activity is often detected at low oxygen concentrations, CH4 oxidation in well-oxygenated downstream rivers below dams has also been reported. Here we combined DNA and RNA high-throughput sequencing with microscopic enumeration (by CARD-FISH) and biogeochemical data to investigate the abundance, composition, and potential activity of MOB taxa from upstream to downstream waters in the tropical hydropower complex Batang Ai (Malaysia). High relative abundance of MOB (up to 61% in 16S rRNA sequences and 19% in cell counts) and enrichment of stable isotopic signatures of CH4 (up to 0‰) were detected in the hypoxic hypolimnion of the reservoir and in the outflowing downstream river. MOB community shifts along the river-reservoir system reflected environmental sorting of taxa and an interrupted hydrologic connectivity in which downstream MOB communities resembled reservoir's hypolimnetic communities but differed from upstream and surface reservoir communities. In downstream waters, CH4 oxidation was accompanied by fast cell growth of particular MOB taxa. Our results suggest that rapid shifts in active MOB communities allow the mitigation of CH4 emissions from different zones of hydropower complexes, including in quickly re-oxygenated rivers downstream of dams.

Matched MeSH terms: RNA, Ribosomal, 16S/genetics
Gene expression changes associated with malignant transformation of oral potentially malignant disorders

Sathasivam HP, Casement J, Bates T, Sloan P, Thomson P, Robinson M, et al.

J Oral Pathol Med, 2021 Jan;50(1):60-67.
PMID: 32740996 DOI: 10.1111/jop.13090

BACKGROUND: A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed "non-transforming" (NT) cases.
METHODS: Total RNA was extracted from formalin-fixed paraffin-embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected P-value was 1.90). Analysis of RNA-Sequencing outputs revealed 41 genes (34 protein-coding; 7 non-coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from -2.63 to 2.48, with 23 protein-coding genes being downregulated and 11 protein-coding genes being upregulated in MT cases compared to NT cases.
CONCLUSION: Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the etiopathogenesis of OPMD and development of novel biomarkers.

Matched MeSH terms: Cell Transformation, Neoplastic/genetics
CYP2C19 Genotype-Guided Antiplatelet Therapy Among Asian Patients with Ischaemic Stroke

Kow CS, Zaihan AF, Hasan SS

Clin Drug Investig, 2021 01;41(1):115-116.
PMID: 33237558 DOI: 10.1007/s40261-020-00985-5
Matched MeSH terms: Cytochrome P-450 CYP2C19/genetics
Unravelling the diagnostic and therapeutic potentialities of a novel RNA aptamer isolated against human pituitary tumour transforming gene 1 (PTTG1) protein

Prabu SS, Ch'ng ES, Woon PY, Chen JH, Tang TH, Citartan M

Anal Chim Acta, 2020 Nov 22;1138:181-190.
PMID: 33161980 DOI: 10.1016/j.aca.2020.09.038

Human Pituitary Tumour Transforming Gene 1 (PTTG1) is an oncoprotein involved in maintaining chromosome stability and acts as a biomarker for a panel of cancers. In this study, we endeavoured to generate an RNA aptamer against PTTG1. The RNA aptamer, SECURA-3 has an estimated equilibrium dissociation constant of 16.41 ± 6.4 nM. The aptamer was successfully harnessed in several diagnostic platforms including ELASA, aptamer-based dot blot and aptamer-based western blot. SECURA-3 was also unveiled as a potential probe that could replace its counterpart antibody in the histostaining-based detection of PTTG1 in HeLa and MCF-7 formalin-fixed paraffin-embedded cell blocks. In the aspect of therapeutics, SECURA-3 RNA aptamer demonstrates an antagonistic effect by antagonizing the interaction between PTTG1 and CXCR2, as revealed in the in vitro competitive nitrocellulose filter binding assay and dual-luciferase reporter assay in HeLa cells. As the first anti-PTTG1 aptamer, SECURA-3 RNA aptamer has immense diagnostic and therapeutic properties.

Matched MeSH terms: Securin/genetics*
Differentiated sap (4-6) gene expression of Candida albicans isolates from HIV-positive patients with oral candidiasis and commensals in healthy individuals

Meylani V, Sembiring L, Fudholi A, Wibawa T

Microb Pathog, 2021 Sep;158:105075.
PMID: 34224845 DOI: 10.1016/j.micpath.2021.105075

Gene expression of SAP 4-6 based on the detection of mRNA was observed in Candida albicans isolates from HIV-positive patients with oral candidiasis and commensal from healthy individuals. The species of C. albicans strains were selectively isolated from both sources using CHROMagar Chromogenic Media. The obtained isolates were then induced to express SAP 4-6 using SAP 4-6 gene inducer media. Analysis of gene expression was performed on a molecular basis using the RT-PCR method. Molecular analysis of gene expression showed that the isolates CH3 from HIV-positive patients with oral candidiasis could express SAP 4-6 gene, while commensal isolates from healthy people could not. Based on the results of this study, it could be concluded that, in terms of molecular detection, only isolates from HIV-positive patients (CH3) could express their SAP 4-6 gene.

Matched MeSH terms: Candida albicans/genetics
Fulltext Noonan syndrome in diverse populations

Kruszka P, Porras AR, Addissie YA, Moresco A, Medrano S, Mok GTK, et al.

Am J Med Genet A, 2017 Sep;173(9):2323-2334.
PMID: 28748642 DOI: 10.1002/ajmg.a.38362

Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.

Matched MeSH terms: Genetics, Population*; Noonan Syndrome/genetics*; ras Proteins/genetics; Mitogen-Activated Protein Kinase Kinases/genetics; African Continental Ancestry Group/genetics; European Continental Ancestry Group/genetics
Genetic architecture of Al3+ toxicity tolerance in rice F2:3 populations determined through QTL mapping

Jahan N, Javed MA, Khan A, Manan FA, Tabassum B

Ecotoxicology, 2021 Jul;30(5):794-805.
PMID: 33871748 DOI: 10.1007/s10646-021-02413-6

Aluminum (Al3+) toxicity is one of the factors limiting crop production in acidic soils. Identifying quantitative trait loci (QTLs)/genes for tolerance to Al3+ toxicity at seed germination can aid the development of new tolerant cultivars. The segregating population derived from Pak Basmati (Indica) × Pokkali (Indica) was used for mapping QTLs linked with tolerance to Al3+ toxicity ranging from 0 to 20 mM at pH 4 ± 0.2 at germination. The favorable alleles for all new QTLs were analyzed based on germination traits, i.e., final germination percentage (FG%), germination energy (GE), germination speed (GS), germination index (GI), mean germination time (MGT), germination value (GV), germination velocity (GVe), peak value of germination (GPV), and germination capacity (GC), and growth traits, such as root length (RL), shoot length (SL), total dry biomass (TDB) and germination vigor index (GVI). The phenotypic evolution showed transgressive variations. For genome-wide mapping, 90 polymorphic SSRs with 4 gene-specific markers and Win QTL Cart were used for QTL analysis. In all, 35 QTLs for germination and 11 QTLs for seedling growth were detected in distinct chromosomal regions by composite interval mapping (CIM), and multiple interval mapping (MIM) confirmed the pleiotropy at region RM128 on chromosome 1. Based on our genetic mapping studies, the genes/QTLs underlying tolerance to Al3+ toxicity could differ for both the germination and seedling stages in segregated populations. The QTLs identified in this study could be a source of new alleles for improving tolerance to Al3+ toxicity in rice.

Matched MeSH terms: Seedlings/genetics
Regulation of Glycine Cleavage and Detoxification by a Highly Conserved Glycine Riboswitch in Burkholderia spp

Munyati-Othman N, Appasamy SD, Damiri N, Emrizal R, Alipiah NM, Ramlan EI, et al.

Curr Microbiol, 2021 Aug;78(8):2943-2955.
PMID: 34076709 DOI: 10.1007/s00284-021-02550-5

The glycine riboswitch is a known regulatory element that is unique in having two aptamers that are joined by a linker region. In this study, we investigated a glycine riboswitch located in the 5' untranslated region of a glycine cleavage system homolog (gcvTHP) in Burkholderia spp. Structure prediction using the sequence generated a model with a glycine binding pocket composed of base-triple interactions (G62-A64-A86 and G65-U84-C85) that are supported by A/G minor interactions (A17-C60-G88 and G16-C61-G87, respectively) and two ribose-zipper motifs (C11-G12 interacting with A248-A247 and C153-U154 interacting with A79-A78) which had not been previously reported. The capacity of the riboswitch to bind to glycine was experimentally validated by native gel assays and the crucial role of interactions that make up the glycine binding pocket were proven by mutations of A17U and G16C which resulted in conformational differences that may lead to dysfunction. Using glycine supplemented minimal media, we were able to prove that the expression of the gcvTHP genes found downstream of the riboswitch responded to the glycine concentrations introduced thus confirming the role of this highly conserved Burkholderia riboswitch and its associated genes as a putative glycine detoxification system in Burkholderia spp.

Matched MeSH terms: Glycine/genetics
Fulltext The Crown Pearl: a draft genome assembly of the European freshwater pearl mussel Margaritifera margaritifera (Linnaeus, 1758)

Gomes-Dos-Santos A, Lopes-Lima M, Machado AM, Marcos Ramos A, Usié A, Bolotov IN, et al.

DNA Res, 2021 May 02;28(2).
PMID: 33755103 DOI: 10.1093/dnares/dsab002

Since historical times, the inherent human fascination with pearls turned the freshwater pearl mussel Margaritifera margaritifera (Linnaeus, 1758) into a highly valuable cultural and economic resource. Although pearl harvesting in M. margaritifera is nowadays residual, other human threats have aggravated the species conservation status, especially in Europe. This mussel presents a myriad of rare biological features, e.g. high longevity coupled with low senescence and Doubly Uniparental Inheritance of mitochondrial DNA, for which the underlying molecular mechanisms are poorly known. Here, the first draft genome assembly of M. margaritifera was produced using a combination of Illumina Paired-end and Mate-pair approaches. The genome assembly was 2.4 Gb long, possessing 105,185 scaffolds and a scaffold N50 length of 288,726 bp. The ab initio gene prediction allowed the identification of 35,119 protein-coding genes. This genome represents an essential resource for studying this species' unique biological and evolutionary features and ultimately will help to develop new tools to promote its conservation.

Matched MeSH terms: Bivalvia/genetics*
Fulltext Classical and alternative receptors for SARS-CoV-2 therapeutic strategy

Masre SF, Jufri NF, Ibrahim FW, Abdul Raub SH

Rev Med Virol, 2021 09;31(5):1-9.
PMID: 33368788 DOI: 10.1002/rmv.2207

Understanding the molecules that are essential for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) entry can provide insights into viral infection and dissemination. Recently, it has been identified from several studies that angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 are the main entry molecules for the SARS-CoV-2, which produced the pandemic of Covid-19. However, additional evidence showed several other viral receptors and cellular proteases that are also important in facilitating viral entry and transmission in the target cells. In this review, we summarized the types of SARS-CoV-2 entry molecules and discussed their crucial roles for virus binding, protein priming and fusion to the cellular membrane important for SARS-CoV-2 infection.

Matched MeSH terms: Receptors, Virus/genetics
Fulltext Comparative genome analyses of mycobacteria give better insights into their evolution

Wee WY, Dutta A, Choo SW

PLoS One, 2017;12(3):e0172831.
PMID: 28291784 DOI: 10.1371/journal.pone.0172831

Mycobacteria a genus of Actinobacteria are widespread in nature ranging from soil-dwelling saprophytes to human and animal pathogens. The rate of growth has been a classifying factor for the Mycobacterium spp., dividing them into the rapid growers and the slow growers. Here we have performed a comparative genome study of mycobacterial species in order to get better understanding of their evolution, particularly to understand the distinction between the rapid and slow growers. Our study shows that the slow growers had generally gained and lost more genes compared to the rapid growers. The slow growers might haved eventually lost genes (LivFGMH operon, shaACDEFG genes and MspA porin) that could contribute to the slow growth rate of the slow growers. The genes gained and lost in mycobacteria had eventually helped these bacteria to adapt to different environments and have led to the evolution of the present day rapid and slow growers. Our results also show high number of Mycobacterium abscessus specific genes (811 genes) and some of them are associated with the known bacterial quorum sensing genes that might be important for Mycobacterium abscessus to adapt and survive in variety of unfavorable environments. Mycobacterium abscessus also does not contains genes involved in the bacterial defense system and together with the quorum sensing genes may have contributed to the high gene gain rate of Mycobacterium abscessus.

Matched MeSH terms: Mycobacterium/genetics*
HAPTOGLOBIN AND TRANSFERRIN STUDIES IN MALAYSIA

CHIN J

Med J Malaysia, 1964 Sep;19:71-2.
PMID: 14240067
Matched MeSH terms: Genetics, Medical*
Interaction of haemoglobin E with alpha-thalassaemia and haemoglobin Constant Spring

Ganesan J, Lie-Injo LE, Ng TS, George R

Acta Haematol., 1977;57(2):109-15.
PMID: 402765 DOI: 10.1159/000207867

The combination of Hb E,alpha-thalassaemia and Hb CoSp was found in a 20-year-old female Malay who presented with a moderately severe haemolytic anaemia. The findings in the patient and her family from which this diagnosis was arrived at are discussed. Although this is the first report of this condition in this country it is pointed out that one may see more such cases in the future if one is aware of this condition since Hb E, alpha-thalassaemia and Hb CoSp all occur at significant frequencies in this country.

Matched MeSH terms: Thalassemia/genetics*
A family with testicular feminisation

Boon WH, Salmon Y, Seng CT

Med J Malaya, 1966 Sep;21(1):56-62.
PMID: 4224879
Matched MeSH terms: Disorders of Sex Development/genetics*
A survey of recently emerged genome-wide computational enhancer predictor tools

Lim LWK, Chung HH, Chong YL, Lee NK

Comput Biol Chem, 2018 Jun;74:132-141.
PMID: 29602043 DOI: 10.1016/j.compbiolchem.2018.03.019

The race for the discovery of enhancers at a genome-wide scale has been on since the commencement of next generation sequencing decades after the discovery of the first enhancer, SV40. A few enhancer-predicting features such as chromatin feature, histone modifications and sequence feature had been implemented with varying success rates. However, to date, there is no consensus yet on the single enhancer marker that can be employed to ultimately distinguish and uncover enhancers from the enormous genomic regions. Many supervised, unsupervised and semi-supervised computational approaches had emerged to complement and facilitate experimental approaches in enhancer discovery. In this review, we placed our focus on the recently emerged enhancer predictor tools that work on general enhancer features such as sequences, chromatin states and histone modifications, eRNA and of multiple feature approach. Comparisons of their prediction methods and outcomes were done across their functionally similar counterparts. We provide some recommendations and insights for future development of more comprehensive and robust tools.

Matched MeSH terms: Enhancer Elements, Genetic/genetics*
Escherichia coli tolerance of ultraviolet radiation by in vivo expression of a short peptide designed from late embryogenesis abundant protein

Huwaidi A, Pathak N, Syahir A, Ikeno S

Biochem Biophys Res Commun, 2018 09 05;503(2):910-914.
PMID: 29928878 DOI: 10.1016/j.bbrc.2018.06.095

Ultraviolet (UV) radiation causes damage in all living organisms, including DNA damage that leads to cell death. Herein, we provide a new technique for UV radiation protection through intracellular short peptide expression. The late embryogenesis abundant (LEA) peptide, which functions as a shield that protects macromolecules from various abiotic stress, was obtained from the Polypedilum vanderplanki group 3 LEA protein. Recombinant Escherichia coli BL21 (DE3) expressing functional LEA short peptide in vivo were exposed to UVA and UVC radiation for 4, 6, and 8 h. E. coli transformants expressing the LEA peptide showed higher cell viability under both UVA and UVC treatment at all time points as compared with that of the control. Furthermore, the cells expressing LEA peptide showed a higher number of colony-forming units per dilution under UVA and UVC treatment. These results suggested that expression of the short peptide could be useful for the development of genetically modified organisms and in applications that require resilience of organisms to UV radiation.

Matched MeSH terms: Adaptation, Physiological/genetics; Chironomidae/genetics; Escherichia coli/genetics; Peptides/genetics*; Transgenes/genetics; Insect Proteins/genetics*; Microbial Viability/genetics
Renin-Angiotensin-Aldosterone System Gene Polymorphisms and Type 2 Diabetic Nephropathy in Asian Populations: An Updated Meta-analysis

Ahmad N, Jamal R, Shah SA, Gafor AHA, Murad NAA

Curr Diabetes Rev, 2019;15(4):263-276.
PMID: 29984662 DOI: 10.2174/1573399814666180709100411

BACKGROUND: The association of polymorphisms in the renin-angiotensin-aldosterone system candidate genes, namely Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D), Angiotensinogen (AGT) M235T and Angiotensin II Receptor Type 1 (AGTR1) A1166C with Diabetic Nephropathy (DN) has been studied for decades.
OBJECTIVE: This meta-analysis aimed to assess the updated pooled effects of these polymorphisms with DN among Asian populations with type 2 diabetes mellitus.
METHODS: The PubMed electronic database was searched without duration filter until August 2017 and the reference list of eligible studies was screened. The association of each polymorphism with DN was examined using odds ratio and its 95% confidence interval based on dominant, recessive and allele models. Subgroup analyses were conducted based on region, DN definition and DM duration.
RESULTS: In the main analysis, the ACE I/D (all models) and AGTR1 A1166C (dominant model) showed a significant association with DN. The main analysis of the AGT M235T polymorphism did not yield significant findings. There were significant subgroup differences and indication of significantly higher odds for DN in terms of DM duration (≥10 years) for ACE I/D (all models), AGT M235T (recessive and allele models) and AGTR1 A1166C (recessive model). Significant subgroup differences were also observed for DN definition (advanced DN group) and region (South Asia) for AGTR1 A1166C (recessive model).
CONCLUSION: In the Asian populations, ACE I/D and AGTR1 A1166C may contribute to DN susceptibility in patients with T2DM by different genetic models. However, the role of AGT M235T needs to be further evaluated.

Matched MeSH terms: Angiotensinogen/genetics; Diabetes Mellitus, Type 2/genetics*; Diabetic Nephropathies/genetics*; Peptidyl-Dipeptidase A/genetics; Renin-Angiotensin System/genetics*; Receptor, Angiotensin, Type 1/genetics; Asian Continental Ancestry Group/genetics
Fulltext Selective activation of miRNAs of the primate-specific chromosome 19 miRNA cluster (C19MC) in cancer and stem cells and possible contribution to regulation of apoptosis

Nguyen PN, Huang CJ, Sugii S, Cheong SK, Choo KB

J Biomed Sci, 2017 Mar 07;24(1):20.
PMID: 28270145 DOI: 10.1186/s12929-017-0326-z

BACKGROUND: The human chromosome 19 miRNA cluster (C19MC) of 43 genes is a primate-specific miRNA cluster that may have biological significance in the genetic complexity of the primate. Despite previous reports on individual C19MC miRNA expression in cancer and stem cells, systematic studies on C19MC miRNA expression and biological functions are lacking.
RESULTS: Cluster-wide C19MC miRNA expression profiling by microarray analysis showed wholesome C19MC activation in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, in multipotent adipose-derived mesenchymal stem cells (MSCs) and a unipotent human white pre-adipocyte cell line, only selected C19MC miRNAs were expressed. MiRNA copy number analysis also showed selective C19MC expression in cancer cells with expression patterns highly similar to those in MSCs, suggesting similar miRNA regulatory mechanisms in these cells. Selective miRNA expression also suggests complex transcriptional mechanism(s) regulating C19MC expression under specific cellular and pathological conditions. Bioinformatics analysis showed that sixteen of the C19MC miRNAs share the same "AAGUGC" seed sequence with members of the miR-302/-372 family, which are known cellular reprogramming factors. In particular, C19MC-AAGUGC-miRNAs with the nucleotides 2-7 canonical seed position as in miR-302/-372 miRNAs, may play similar roles as miR-302/-372 in induced pluripotency. A biased 3p-arm selection of the C19MC-AAGUGC-miRNAs was observed indicating that targets of the 3p species of these miRNAs may be biologically significant in regulating stemness. Furthermore, bioinformatics analysis of the putative targets of the C19MC-AAGUGC-miRNAs predicted significant involvement of signaling pathways in reprogramming, many of which contribute to promoting apoptosis by indirect activation of the pro-apoptotic proteins BAK/BAX via suppression of genes of the cell survival pathways, or by enhancing caspase-8 activation through targeting inhibitors of TRAIL-inducing apoptosis.
CONCLUSIONS: This work demonstrated selective C19MC expression in MSCs and cancer cells, and, through miRNA profiling and bioinformatics analysis, predicted C19MC modulation of apoptosis in induced pluripotency and tumorigenesis.

Matched MeSH terms: Chromosomes, Human, Pair 19/genetics; Neoplasms/genetics*; Primates/genetics; Apoptosis/genetics*; MicroRNAs/genetics; DNA Copy Number Variations/genetics; Carcinogenesis/genetics*

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