Displaying publications 141 - 160 of 1023 in total

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  1. Prospective Advances in Circular RNA Investigation
    Sulaiman SA, Abdul Murad NA, Mohamad Hanif EA, Abu N, Jamal R
    Adv Exp Med Biol, 2018 9 28;1087:357-370.
    PMID: 30259380 DOI: 10.1007/978-981-13-1426-1_28
    circRNAs have emerged as one of the key regulators in many cellular mechanisms and pathogenesis of diseases. However, with the limited knowledge and current technologies for circRNA investigations, there are several challenges that need to be addressed for. These include challenges in understanding the regulation of circRNA biogenesis, experimental designs, and sample preparations to characterize the circRNAs in diseases as well as the bioinformatics pipelines and algorithms. In this chapter, we discussed the above challenges and possible strategies to overcome those limitations. We also addressed the differences between the existing applications and technologies to study the circRNAs in diseases. By addressing these challenges, further understanding of circRNAs roles and regulations as well as the discovery of novel circRNAs could be achieved.
    Matched MeSH terms: Gene Expression Regulation/genetics
  2. Identification and expression profiling of genes governing lignin biosynthesis in Casuarina equisetifolia L
    Vikashini B, Shanthi A, Ghosh Dasgupta M
    Gene, 2018 Nov 15;676:37-46.
    PMID: 30201104 DOI: 10.1016/j.gene.2018.07.012
    Casuarina equisetifolia L. is an important multi-purpose, fast growing and widely planted tree species native to tropical and subtropical coastlines of Australia, Southeast Asia, Malaysia, Melanesia, Polynesia and New Caledonia. It is a nitrogen-fixing tree mainly used for charcoal making, construction poles, landscaping, timber, pulp, firewood, windbreaks, shelterbelts, soil erosion and sand dune stabilization. Casuarina wood is presently used for paper and pulp production. Raw material with reduced lignin is highly preferred to increase the pulp yield. Hence, understanding the molecular regulation of wood formation in this tree species is vital for selecting industrially suitable phenotypes for breeding programs. The lignin biosynthetic pathway has been extensively studied in tree species like Eucalypts, poplars, pines, Picea, Betula and Acacia sp. However, studies on wood formation at molecular level is presently lacking in casuarinas. Hence, in the present study, the transcriptome of the developing secondary tissues of 15 years old Casuarina equiseitfolia subsp. equisetifolia was sequenced, de novo assembled, annotated and mapped to functional pathways. Transcriptome sequencing generated a total of 26,985 transcripts mapped to 31 pathways. Mining of the annotated data identified nine genes involved in lignin biosynthesis pathway and relative expression of the transcripts in four tissues including scale-like leaves, needle-like brachlets, wood and root were documented. The expression of CeCCR1 and CeF5H were found to be significantly high in wood tissues, while maximum expression of CeHCT was documented in stem. Additionally, CeTUBA and CeH2A were identified as the most stable reference transcript for normalization of qRT-PCR data in C. equisetifolia. The present study is the first wood genomic resource in C. equisetifolia, which will be valuable for functional genomics research in this genus.
    Matched MeSH terms: Gene Expression Regulation, Plant/genetics
  3. Differential expression of heat shock and floral regulatory genes in pseudocarpel initials of mantled female inflorescences from Elaeis guineensis Jacq
    Ooi SE, Sarpan N, Abdul Aziz N, Nuraziyan A, Ong-Abdullah M
    Plant Reprod, 2019 06;32(2):167-179.
    PMID: 30467592 DOI: 10.1007/s00497-018-0350-5
    KEY MESSAGE: Transcriptomes generated by laser capture microdissected abnormal staminodes revealed adoption of carpel programming during organ initiation with decreased expression of numerousHSPs,EgDEF1, EgGLO1but increasedLEAFYexpression. The abnormal mantled phenotype in oil palm involves a feminization of the male staminodes into pseudocarpels in pistillate inflorescences. Previous studies on oil palm flowering utilized entire inflorescences or spikelets, which comprised not only the male and female floral organs, but the surrounding tissues as well. Laser capture microdissection coupled with RNA sequencing was conducted to investigate the specific transcriptomes of male and female floral organs from normal and mantled female inflorescences. A higher number of differentially expressed genes (DEGs) were identified in abnormal versus normal male organs compared with abnormal versus normal female organs. In addition, the abnormal male organ transcriptome closely mimics the transcriptome of abnormal female organ. While the transcriptome of abnormal female organ was relatively similar to the normal female organ, a substantial amount of female DEGs encode HEAT SHOCK PROTEIN genes (HSPs). A similar high amount (20%) of male DEGs encode HSPs as well. As these genes exhibited decreased expression in abnormal floral organs, mantled floral organ development may be associated with lower stress indicators. Stamen identity genes EgDEF1 and EgGLO1 were the main floral regulatory genes with decreased expression in abnormal male organs or pseudocarpel initials. Expression of several floral transcription factors was elevated in pseudocarpel initials, notably LEAFY, FIL and DL orthologs, substantiating the carpel specification programming of abnormal staminodes. Specific transcriptomes thus obtained through this approach revealed a host of differentially regulated genes in pseudocarpel initials compared to normal male staminodes.
    Matched MeSH terms: Gene Expression Regulation, Plant/genetics*
  4. Arabidopsis Group IIId ERF proteins positively regulate primary cell wall-type CESA genes
    Saelim L, Akiyoshi N, Tan TT, Ihara A, Yamaguchi M, Hirano K, et al.
    J Plant Res, 2019 Jan;132(1):117-129.
    PMID: 30478480 DOI: 10.1007/s10265-018-1074-1
    The cell wall determines morphology and the environmental responses of plant cells. The primary cell wall (PCW) is produced during cell division and expansion, determining the cell shape and volume. After cell expansion, specific types of plant cells produce a lignified wall, known as a secondary cell wall (SCW). We functionally analyzed Group IIId Arabidopsis AP2/EREBP genes, namely ERF34, ERF35, ERF38, and ERF39, which are homologs of a rice ERF gene previously proposed to be related to SCW biosynthesis. Expression analysis revealed that these four genes are expressed in regions related to cell division and/or cell differentiation in seedlings (i.e., shoot apical meristems, the primordia of leaves and lateral roots, trichomes, and central cylinder of primary roots) and flowers (i.e., vascular tissues of floral organs and replums and/or valve margins of pistils). Overexpression of ERF genes significantly upregulated PCW-type, but not SCW-type, CESA genes encoding cellulose synthase catalytic subunits in Arabidopsis seedlings. Transient co-expression reporter analysis indicated that ERF35, ERF38, and ERF39 possess transcriptional activator activity, and that ERF34, ERF35, ERF38, and ERF39 upregulated the promoter activity of CESA1, a PCW-type CESA gene, through the DRECRTCOREAT elements, the core cis-acting elements known to be recognized by AP2/ERF proteins. Together, our findings show that Group IIId ERF genes are positive transcriptional regulators of PCW-type CESA genes in Arabidopsis and are possibly involved in modulating cellulose biosynthesis in response to developmental requirements and environmental stimuli.
    Matched MeSH terms: Gene Expression Regulation, Plant*
  5. HMGB1: an overview of its versatile roles in the pathogenesis of colorectal cancer
    Cheng KJ, Alshawsh MA, Mejia Mohamed EH, Thavagnanam S, Sinniah A, Ibrahim ZA
    Cell Oncol (Dordr), 2020 Apr;43(2):177-193.
    PMID: 31677065 DOI: 10.1007/s13402-019-00477-5
    BACKGROUND: In recent years, the high mobility group box-1 (HMGB1) protein, a damage-associated molecular pattern (DAMP) molecule, has been found to play multifunctional roles in the pathogenesis of colorectal cancer. Although much attention has been given to the diagnostic and prognostic values of HMGB1 in colorectal cancer, the exact functional roles of the protein as well as the mechanistic pathways involved have remained poorly defined. This systematic review aims to discuss what is currently known about the roles of HMGB1 in colorectal cancer development, growth and progression, and to highlight critical areas for future investigations. To achieve this, the bibliographic databases Pubmed, Scopus, Web of Science and ScienceDirect were systematically screened for articles from inception till June 2018, which address associations of HMGB1 with colorectal cancer.

    CONCLUSIONS: HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  6. Gut bacteria characteristic of the infant microbiota down-regulate inflammatory transcriptional responses in HT-29 cells
    Pathmanathan SG, Lawley B, McConnell M, Baird MA, Tannock GW
    Anaerobe, 2020 Feb;61:102112.
    PMID: 31629806 DOI: 10.1016/j.anaerobe.2019.102112
    Immuno-modulatory effects of infant gut bacteria were tested on poly(I:C) stimulated HT-29 intestinal epithelial cells. Blautia producta, Bacteroides vulgatus, Bacteroides fragilis and Bacteroides thetaiotaomicron decreased transcription of poly(I:C)-induced inflammatory genes. Modulation of basal level and poly(I:C)-induced IL-8 secretion varied between bacterial species, and between heat treated and non-heat treated bacterial cells.
    Matched MeSH terms: Gene Expression Regulation*
  7. Functional characterization of two variants in the 3'-untranslated region (UTR) of transcription factor 4 gene and their association with schizophrenia in sib-pairs from multiplex families
    Mohamed ZI, Tee SF, Chow TJ, Loh SY, Yong HS, Bakar AKA, et al.
    Asian J Psychiatr, 2019 Feb;40:76-81.
    PMID: 30771755 DOI: 10.1016/j.ajp.2019.02.001
    Transcription factor 4 (TCF4) gene plays an important role in nervous system development and it always associated with the risk of schizophrenia. Since miRNAs regulate targetgenes by binding to 3'UTRs of target mRNAs, the functional variants located in 3'UTR of TCF4 are highly suggested to affect the gene expressions in schizophrenia. To test the hypothesis regarding the effects of the variants located in 3'UTR of TCF4, we conducted an in silico analysis to identify the functional variants and their predicted functions. In this study, we sequenced the 3'UTR of TCF4 in 13 multiplex schizophrenia families and 14 control families. We found two functional variants carried by three unrelated patients. We determined that the C allele of rs1272363 and the TC insert of rs373174214 might suppress post- transcriptional expression. Secondly, we cloned the region that flanked these two variants into a dual luciferase reporter system and compared the luciferase activities between the pmirGLO-TCF4 (control), pmirGLO-TCF4-rs373174214 and pmirGLO-TCF4-rs1273263. Both pmirGLO-TCF4-rs373174214 and pmirGLO-TCF4-rs1273263 caused lower reporter gene activities, as compared to the control. However, only the C allele of rs1272363 reduced the luciferase activity significantly (p = 0.0231). Our results suggested that rs1273263 is a potential regulator of TCF4 expression, and might be associated with schizophrenia.
    Matched MeSH terms: Gene Expression Regulation/genetics*
  8. Characterization of Oil Palm Acyl-CoA-Binding Proteins and Correlation of Their Gene Expression with Oil Synthesis
    Amiruddin N, Chan PL, Azizi N, Morris PE, Chan KL, Ong PW, et al.
    Plant Cell Physiol, 2020 Apr 01;61(4):735-747.
    PMID: 31883014 DOI: 10.1093/pcp/pcz237
    Acyl-CoA-binding proteins (ACBPs) are involved in binding and trafficking acyl-CoA esters in eukaryotic cells. ACBPs contain a well-conserved acyl-CoA-binding domain. Their various functions have been characterized in the model plant Arabidopsis and, to a lesser extent, in rice. In this study, genome-wide detection and expression analysis of ACBPs were performed on Elaeis guineensis (oil palm), the most important oil crop in the world. Seven E. guineensis ACBPs were identified and classified into four groups according to their deduced amino acid domain organization. Phylogenetic analysis showed conservation of this family with other higher plants. All seven EgACBPs were expressed in most tissues while their differential expression suggests various functions in specific tissues. For example, EgACBP3 had high expression in inflorescences and stalks while EgACBP1 showed strong expression in leaves. Because of the importance of E. guineensis as an oil crop, expression of EgACBPs was specifically examined during fruit development. EgACBP3 showed high expression throughout mesocarp development, while EgACBP1 had enhanced expression during rapid oil synthesis. In endosperm, both EgACBP1 and EgACBP3 exhibited increased expression during seed development. These results provide important information for further investigations on the biological functions of EgACBPs in various tissues and, in particular, their roles in oil synthesis.
    Matched MeSH terms: Gene Expression Regulation, Plant*
  9. Angiogenesis regulation by microRNAs and long non-coding RNAs in human breast cancer
    Chong ZX, Yeap SK, Ho WY
    Pathol Res Pract, 2021 Mar;219:153326.
    PMID: 33601152 DOI: 10.1016/j.prp.2020.153326
    MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are capable of regulating gene expression post-transcriptionally. Since the past decade, a number of in vitro, in vivo, and clinical studies reported the roles of these non-coding RNAs (ncRNAs) in regulating angiogenesis, an important cancer hallmark that is associated with metastases and poor prognosis. The specific roles of various miRNAs and lncRNAs in regulating angiogenesis in breast cancer, with particular focus on the downstream targets and signalling pathways regulated by these ncRNAs will be discussed in this review. In light of the recent trend in exploiting ncRNAs as cancer therapeutics, the potential use of miRNAs and lncRNAs as biomarkers and novel therapeutic agent against angiogenesis was also discussed.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/genetics*
  10. Cytokine Induction in Nipah Virus-Infected Primary Human and Porcine Bronchial Epithelial Cells
    Elvert M, Sauerhering L, Maisner A
    J Infect Dis, 2020 05 11;221(Suppl 4):S395-S400.
    PMID: 31665348 DOI: 10.1093/infdis/jiz455
    During the Nipah virus (NiV) outbreak in Malaysia, pigs and humans were infected. While pigs generally developed severe respiratory disease due to effective virus replication and associated inflammation processes in porcine airways, respiratory symptoms in humans were rare and less severe. To elucidate the reasons for the species-specific differences in NiV airway infections, we compared the cytokine responses as a first reaction to NiV in primary porcine and human bronchial epithelial cells (PBEpC and HBEpC, respectively). In both cell types, NiV infection resulted in the expression of type III interferons (IFN-λ). Upon infection with similar virus doses, viral RNA load and IFN expression were substantially higher in HBEpC. Even if PBEpC expressed the same viral RNA amounts as NiV-infected HBEpC, the porcine cells showed reduced IFN- and IFN-dependent antiviral gene expression. Despite this inherently limited IFN response, the expression of proinflammatory cytokines (IL-6, IL-8) in NiV-infected PBEpC was not decreased. The downregulation of antiviral activity in the presence of a functional proinflammatory cytokine response might be one of the species-specific factors contributing to efficient virus replication and acute inflammation in the lungs of pigs infected with the Malaysian NiV strain.
    Matched MeSH terms: Gene Expression Regulation/immunology
  11. Fulltext Plasma Circulating Mirnas Profiling for Identification of Potential Breast Cancer Early Detection Biomarkers
    Jusoh AR, Mohan SV, Lu Ping T, Tengku Din TADAAB, Haron J, Romli RC, et al.
    Asian Pac J Cancer Prev, 2021 May 01;22(5):1375-1381.
    PMID: 34048164 DOI: 10.31557/APJCP.2021.22.5.1375
    OBJECTIVE: This study aimed to characterize the miRNA expression profiles from plasma samples of our local breast cancer patients in comparison to healthy control by using miRNA PCR Array.

    METHODS: In this study, plasma miRNA profiles from eight early-stage breast cancer patients and nine age-matched (± 2 years) healthy controls were characterized by miRNA array-based approach, followed by differential gene expression analysis, Independent T-test and construction of Receiver Operating Characteristic (ROC) curve to determine the capability of the assays to discriminate between breast cancer and the healthy control.

    RESULTS: Based on the 372-miRNAs microarray profiling, a set of 40 differential miRNAs was extracted regarding to the fold change value at 2 and above. We further sub grouped 40 miRNAs of breast cancer patients that were significantly expressed at 2-fold change and higher. In this set, we discovered that 24 miRNAs were significantly upregulated and 16 miRNAs were significantly downregulated in breast cancer patients, as compared to the miRNA expression of healthy subjects. ROC curve analysis revealed that seven miRNAs (miR-125b-5p, miR-142-3p, miR-145-5p, miR-193a-5p, miR-27b-3p, miR-22-5p and miR-423-5p) had area under curve (AUC) value > 0.7 (AUC p-value < 0.05). Overlapping findings from differential gene expression analysis, ROC analysis, and Independent T-Test resulted in three miRNAs (miR-27b-3p, miR-22-5p, miR-145-5p). Cohen's effect size for these three miRNAs was large with d value are more than 0.95.

    CONCLUSION: miR-27b-3p, miR-22-5p, miR-145-5p could be potential biomarkers to distinguish breast cancer patients from healthy controls. A validation study for these three miRNAs in an external set of samples is ongoing.
    .

    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  12. Fulltext Neuroinflammation as a Key Driver of Secondary Neurodegeneration Following Stroke?
    Stuckey SM, Ong LK, Collins-Praino LE, Turner RJ
    Int J Mol Sci, 2021 Dec 03;22(23).
    PMID: 34884906 DOI: 10.3390/ijms222313101
    Ischaemic stroke involves the rapid onset of focal neurological dysfunction, most commonly due to an arterial blockage in a specific region of the brain. Stroke is a leading cause of death and common cause of disability, with over 17 million people worldwide suffering from a stroke each year. It is now well-documented that neuroinflammation and immune mediators play a key role in acute and long-term neuronal tissue damage and healing, not only in the infarct core but also in distal regions. Importantly, in these distal regions, termed sites of secondary neurodegeneration (SND), spikes in neuroinflammation may be seen sometime after the initial stroke onset, but prior to the presence of the neuronal tissue damage within these regions. However, it is key to acknowledge that, despite the mounting information describing neuroinflammation following ischaemic stroke, the exact mechanisms whereby inflammatory cells and their mediators drive stroke-induced neuroinflammation are still not fully understood. As a result, current anti-inflammatory treatments have failed to show efficacy in clinical trials. In this review we discuss the complexities of post-stroke neuroinflammation, specifically how it affects neuronal tissue and post-stroke outcome acutely, chronically, and in sites of SND. We then discuss current and previously assessed anti-inflammatory therapies, with a particular focus on how failed anti-inflammatories may be repurposed to target SND-associated neuroinflammation.
    Matched MeSH terms: Gene Expression Regulation/drug effects
  13. Seasonal expression and distribution of kisspeptin1 (kiss1) in the ovary and testis of freshwater catfish, Clarias batrachus: A putative role in steroidogenesis
    Singh A, Lal B, Parhar IS, Millar RP
    Acta Histochem, 2021 Sep;123(6):151766.
    PMID: 34384940 DOI: 10.1016/j.acthis.2021.151766
    The central role of kisspeptin (kiss) in mammalian reproduction is well established; however, its intra-gonadal role is poorly addressed. Moreover, studies investigating intra-gonadal role of kiss in fish reproduction are scanty, contradictory and inconclusive. The expression of kiss1 mRNA has been detected in the fish brain, and functionally attributed to the regulation of reproduction, feeding and behavior. The kiss1 mRNA has also been demonstrated in tissues other than the brain in some studies, but its cellular distribution and role at the tissue level have not been adequately addressed in fish. Therefore, an attempt was made in the present study to localize kiss1 in gonadal cells of the freshwater catfish, Clarias batrachus. This study reports the presence of kiss1 in the theca cells and granulosa cells of the ovarian oocytes and interstitial cells in the testis of the catfish. The role of kiss1 in the ovary and testis of the catfish was also investigated using kiss1 receptor (kiss1r) antagonist (p234). The p234 treatment decreased the production of 17β-estradiol in ovary and testosterone in the testis by lowering the activities of 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase under both, in vivo as well as in vitro conditions. The p234 treatment also arrested the progression of oogenesis, as evident from the low number of advancing/advanced oocytes in the treated ovary in comparison to the control ovary. It also reduced the area and perimeter of the seminiferous tubules in the treated catfish testis. Thus, our findings suggest that kiss is involved in the regulation of gonadal steroidogenesis, independent of known endocrine/ autocrine/ paracine regulators, and thereby it accelerates gametogenic processes in the freshwater catfish.
    Matched MeSH terms: Gene Expression Regulation*
  14. Fulltext Bpifcl modulates kiss2 expression under the influence of 11-ketotestosterone in female zebrafish
    Moriya S, Tahsin N, Parhar IS
    Sci Rep, 2017 08 11;7(1):7926.
    PMID: 28801581 DOI: 10.1038/s41598-017-08248-8
    The bactericidal/permeability-increasing (BPI) fold-containing (BPIF) superfamily of genes expressed in the brain are purportedly involved in modulating brain function in response to stress, such as inflammation. Kisspeptin, encoded by kiss, is affected by inflammation in the brain; therefore, BPIF family genes might be involved in the modulation of kisspeptin in the brain. In this study, we investigated the expression of BPIF family C, like (bpifcl) in zebrafish brain and its involvement in kiss2 regulation. The identified, full-length sequence of a bpifcl isoform expressed in the zebrafish brain contained the BPI fold shared by BPIF family members. bpifcl mRNA expression in female zebrafish brains was significantly higher than that in males. Exposure of female zebrafish to 11-ketotestosterone decreased bpifcl and kiss2 mRNA expression. bpifcl knockdown by bpifcl-specific small interfering RNA administration to female zebrafish brain decreased kiss2 mRNA expression. bpifcl expression was widely distributed in the brain, including in the dorsal zone of the periventricular hypothalamus (Hd). Furthermore, bpifcl was also expressed in KISS2 neurons in the Hd. These results suggest that the Bpifcl modulates kiss2 mRNA expression under the influence of testosterone in the Hd of female zebrafish.
    Matched MeSH terms: Gene Expression Regulation*
  15. Effects of acute salt stress on modulation of gene expression in a Malaysian salt-tolerant indigenous rice variety, Bajong
    Yeo BPH, Bhave M, Hwang SS
    J Plant Res, 2018 Jan;131(1):191-202.
    PMID: 28921169 DOI: 10.1007/s10265-017-0977-6
    The small genome size of rice relative to wheat and barley, together with its salt sensitivity, make it an ideal candidate for studies of salt stress response. Transcriptomics has emerged as a powerful technique to study salinity responses in many crop species. By identifying a large number of differentially expressed genes (DEGs) simultaneously after the stress induction, it can provide crucial insight into the immediate responses towards the stressor. In this study, a Malaysian salt-tolerant indigenous rice variety named Bajong and one commercial rice variety named MR219 were investigated for their performance in plant growth and ion accumulation properties after salt stress treatment. Bajong was further investigated for the changes in leaf's transcriptome after 6 h of stress treatment using 100 mM NaCl. Based on the results obtained, Bajong is found to be significantly more salt tolerant than MR219, showing better growth and a lower sodium ion accumulation after the stress treatment. Additionally, Bajong was analysed by transcriptomic sequencing, generating a total of 130 millions reads. The reads were assembled into de novo transcriptome and each transcript was annotated using several pre-existing databases. The transcriptomes of control and salt-stressed samples were then compared, leading to the discovery of 4096 DEGs. Based on the functional annotation results obtained, the enrichment factor of each functional group in DEGs was calculated in relation to the total reads obtained. It was found that the group with the highest gene modulation was involved in the secondary metabolite biosynthesis of plants, with approximately 2.5% increase in relation to the total reads obtained. This suggests an extensive transcriptional reprogramming of the secondary metabolic pathways after stress induction, which could be directly responsible for the salt tolerance capability of Bajong.
    Matched MeSH terms: Gene Expression Regulation, Plant*
  16. Fulltext Cancer stem cells as key drivers of tumour progression
    Ayob AZ, Ramasamy TS
    J Biomed Sci, 2018 Mar 06;25(1):20.
    PMID: 29506506 DOI: 10.1186/s12929-018-0426-4
    BACKGROUND: Cancer stem cells (CSCs) are subpopulations of cancer cells sharing similar characteristics as normal stem or progenitor cells such as self-renewal ability and multi-lineage differentiation to drive tumour growth and heterogeneity. Throughout the cancer progression, CSC can further be induced from differentiated cancer cells via the adaptation and cross-talks with the tumour microenvironment as well as a response from therapeutic pressures, therefore contributes to their heterogeneous phenotypes. Challengingly, conventional cancer treatments target the bulk of the tumour and are unable to target CSCs due to their highly resistance nature, leading to metastasis and tumour recurrence.

    MAIN BODY: This review highlights the roles of CSCs in tumour initiation, progression and metastasis with a focus on the cellular and molecular regulators that influence their phenotypical changes and behaviours in the different stages of cancer progression. We delineate the cross-talks between CSCs with the tumour microenvironment that support their intrinsic properties including survival, stemness, quiescence and their cellular and molecular adaptation in response to therapeutic pressure. An insight into the distinct roles of CSCs in promoting angiogenesis and metastasis has been captured based on in vitro and in vivo evidences.

    CONCLUSION: Given dynamic cellular events along the cancer progression and contributions of resistance nature by CSCs, understanding their molecular and cellular regulatory mechanism in a heterogeneous nature, provides significant cornerstone for the development of CSC-specific therapeutics.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic/physiology*
  17. Fulltext Tert-butylhydroquinone attenuates doxorubicin-induced dysregulation of testicular cytoprotective and steroidogenic genes, and improves spermatogenesis in rats
    Ujah GA, Nna VU, Suleiman JB, Eleazu C, Nwokocha C, Rebene JA, et al.
    Sci Rep, 2021 Mar 09;11(1):5522.
    PMID: 33750916 DOI: 10.1038/s41598-021-85026-7
    Doxorubicin (DOX) is a broad-spectrum chemotherapeutic drug used in the treatment of cancers. It acts by generating reactive oxygen species in target cells. The actions are, however, not limited to cancerous cells as it attacks healthy cells, killing them. This study investigated the benefits of the antioxidant, tert-butylhydroquinone (tBHQ), on testicular toxicity following DOX therapy. Twenty-four adult male albino rats were assigned randomly into four groups (n = 6), namely: normal control (NC), tBHQ, DOX and tBHQ + DOX groups. tBHQ (50 mg/kg body weight in 1% DMSO) was administered orally for 14 consecutive days, while a single DOX dose (7 mg/kg body weight) was administered intraperitoneally on Day 8. DOX decreased sperm count, motility and viability, and decreased the levels of steroidogenesis-related proteins, and reproductive hormones. Furthermore, DOX decreased the expression of antioxidant cytoprotective genes, and decreased the protein level of proliferating cell nuclear antigen in the testis. Conversely, DOX increased the expression of pro-inflammatory and pro-apoptotic genes in the testis. These negative effects were ameliorated following the intervention with tBHQ. Our results suggest that tBHQ protects the testis and preserves both steroidogenesis and spermatogenesis in DOX-treated rats through the suppression of oxidative stress, inflammation and apoptosis.
    Matched MeSH terms: Gene Expression Regulation/drug effects*
  18. Functional characterization of the MSP-C6 promoter as a potential tool for mesocarp-preferential expression of transgenes
    Badai SS, Rasid OA, Masani MYA, Chan KL, Chan PL, Shaharuddin NA, et al.
    J Plant Physiol, 2023 Oct;289:154080.
    PMID: 37699261 DOI: 10.1016/j.jplph.2023.154080
    Modification of lipid composition in the mesocarp tissue of oil palm involves genetic manipulation of multiple genes. More than one mesocarp-preferential promoter is necessary for the expression of individual transgenes in the same plant to obviate transcriptional gene silencing. This study aimed to identify genes that are preferentially expressed in the mesocarp tissue and characterize selected candidate mesocarp-preferential promoters. Ten transcripts that were preferentially expressed in the mesocarp tissue were identified from the analysis of 82 transcriptome datasets of 12 different oil palm tissues. The expression of two candidate genes, MSP-C1 and MSP-C6, was verified to be preferentially expressed in the mesocarp tissues and shown to have a low expression level in non-mesocarp tissues by reverse transcription quantitative real-time PCR (RT-qPCR). MSP-C6 promoter fragments of different lengths were transformed into tomato plants for further characterization. Both unripe and ripe fruits of transgenic tomato plants transformed with a construct harboring the MSP-C6-F1 (2014 bp) promoter were shown to have high beta-glucuronidase (GUS) activities. The findings of this study suggest the potential applications of the MSP-C6 promoter as a molecular tool for genetic engineering of novel traits in fruit crops.
    Matched MeSH terms: Gene Expression Regulation, Plant/genetics
  19. Fulltext Genetic and Global Epigenetic Modification, Which Determines the Phenotype of Transgenic Rice?
    Fan X, Chen J, Wu Y, Teo C, Xu G, Fan X
    Int J Mol Sci, 2020 Mar 06;21(5).
    PMID: 32155767 DOI: 10.3390/ijms21051819
    Transgenic technologies have been applied to a wide range of biological research. However, information on the potential epigenetic effects of transgenic technology is still lacking. Here, we show that the transgenic process can simultaneously induce both genetic and epigenetic changes in rice. We analyzed genetic, epigenetic, and phenotypic changes in plants subjected to tissue culture regeneration, using transgenic lines expressing the same coding sequence from two different promoters in transgenic lines of two rice cultivars: Wuyunjing7 (WYJ7) and Nipponbare (NP). We determined the expression of OsNAR2.1 in two overexpression lines generated from the two cultivars, and in the RNA interference (RNAi) OsNAR2.1 line in NP. DNA methylation analyses were performed on wild-type cultivars (WYJ7 and NP), regenerated lines (CK, T0 plants), segregation-derived wild-type from pOsNAR2.1-OsNAR2.1 (SDWT), pOsNAR2.1-OsNAR2.1, pUbi-OsNAR2.1, and RNAi lines. Interestingly, we observed global methylation decreased in the T0 regenerated line of WYJ7 (CK-WJY7) and pOsNAR2.1-OsNAR2.1 lines but increased in pUbi-OsNAR2.1 and RNAi lines of NP. Furthermore, the methylation pattern in SDWT returned to the WYJ7 level after four generations. Phenotypic changes were detected in all the generated lines except for SDWT. Global methylation was found to decrease by 13% in pOsNAR2.1-OsNAR2.1 with an increase in plant height of 4.69% compared with WYJ7, and increased by 18% in pUbi-OsNAR2.1 with an increase of 17.36% in plant height compared with NP. This suggests an absence of a necessary link between global methylation and the phenotype of transgenic plants with OsNAR2.1 gene over-expression. However, epigenetic changes can influence phenotype during tissue culture, as seen in the massive methylation in CK-WYJ7, T0 regenerated lines, resulting in decreased plant height compared with the wild-type, in the absence of a transformed gene. We conclude that in the transgenic lines the phenotype is mainly determined by the nature and function of the transgene after four generations of transformation, while the global epigenetic modification is dependent on the genetic background. Our research suggests an innovative insight in explaining the reason behind the occurrence of transgenic plants with random and undesirable phenotypes.
    Matched MeSH terms: Gene Expression Regulation, Plant*
  20. Fulltext RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response
    Konopacka A, Greenwood M, Loh SY, Paton J, Murphy D
    Elife, 2015 Nov 12;4.
    PMID: 26559902 DOI: 10.7554/eLife.09656
    In response to an osmotic challenge, the synthesis of the antidiuretic hormone arginine vasopressin (AVP) increases in the hypothalamus, and this is accompanied by extension of the 3' poly(A) tail of the AVP mRNA, and the up-regulation of the expression of RNA binding protein Caprin-2. Here we show that Caprin-2 binds to AVP mRNAs, and that lentiviral mediated shRNA knockdown of Caprin-2 in the osmotically stimulated hypothalamus shortens the AVP mRNA poly(A) tail at the same time as reducing transcript abundance. In a recapitulated in vitro system, we confirm that Caprin-2 over-expression enhances AVP mRNA abundance and poly(A) tail length. Importantly, we show that Caprin-2 knockdown in the hypothalamus decreases urine output and fluid intake, and increases urine osmolality, urine sodium concentration, and plasma AVP levels. Thus Caprin-2 controls physiological mechanisms that are essential for the body's response to osmotic stress.
    Matched MeSH terms: Gene Expression Regulation*
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