Displaying publications 1 - 20 of 116 in total

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  1. Identification of differentially expressed circular RNAs in chemoresistant colorectal cancer
    Abu N, Hon KW, Jeyaraman S, Yahaya A, Abdullah NM, Mustangin M, et al.
    Epigenomics, 2019 06;11(8):875-884.
    PMID: 31020847 DOI: 10.2217/epi-2019-0042
    Aim: Chemoresistance in colorectal cancer (CRC) has become a burden in treating the disease effectively. Circular RNAs (circRNAs) are a type of noncoding RNA that were found to be important in cellular homeostasis. The involvement of circRNAs in relation to chemoresistance in other types of cancers has also been reported. This study aims to identify the differentially expressed circRNAs between chemoresistant and chemosensitive CRC cells. Materials & methods: We developed a chemoresistant cell line model and profiled the circRNAs via microarray. We further validated the expression of two circRNAs in 25 formalin-fixed paraffin-embedded (FFPE) tissue specimens (13 nonresponders and 12 responders) via quantitative polymerase chain reaction (qPCR).  Results & conclusion: We found that there were 773 upregulated and 732 downregulated circRNAs between the chemoresistant and chemosensitive HCT-116 cells. We found that hsa_circ_32883 could be a promising biotarget.
    Matched MeSH terms: MicroRNAs/genetics*
  2. Fulltext Advancements in reprogramming strategies for the generation of induced pluripotent stem cells
    Lai MI, Wendy-Yeo WY, Ramasamy R, Nordin N, Rosli R, Veerakumarasivam A, et al.
    J Assist Reprod Genet, 2011 Apr;28(4):291-301.
    PMID: 21384252 DOI: 10.1007/s10815-011-9552-6
    Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells has emerged as an invaluable method for generating patient-specific stem cells of any lineage without the use of embryonic materials. Following the first reported generation of iPS cells from murine fibroblasts using retroviral transduction of a defined set of transcription factors, various new strategies have been developed to improve and refine the reprogramming technology. Recent developments provide optimism that the generation of safe iPS cells without any genomic modification could be derived in the near future for the use in clinical settings. This review summarizes current and evolving strategies in the generation of iPS cells, including types of somatic cells for reprogramming, variations of reprogramming genes, reprogramming methods, and how the advancement iPS cells technology can lead to the future success of reproductive medicine.
    Matched MeSH terms: MicroRNAs/genetics
  3. Fulltext Differential expression of basal microRNAs' patterns in human dental pulp stem cells
    Vasanthan P, Govindasamy V, Gnanasegaran N, Kunasekaran W, Musa S, Abu Kasim NH
    J Cell Mol Med, 2015 Mar;19(3):566-80.
    PMID: 25475098 DOI: 10.1111/jcmm.12381
    MicroRNAs (miRNAs) are small non-coding RNAs that regulate translation of mRNA into protein and play a crucial role for almost all biological activities. However, the identification of miRNAs from mesenchymal stem cells (MSCs), especially from dental pulp, is poorly understood. In this study, dental pulp stem cells (DPSCs) were characterized in terms of their proliferation and differentiation capacity. Furthermore, 104 known mature miRNAs were profiled by using real-time PCR. Notably, we observed 19 up-regulated miRNAs and 29 significantly down-regulated miRNAs in DPSCs in comparison with bone marrow MSCs (BM-MSCs). The 19 up-regulated miRNAs were subjected to ingenuity analysis, which were composed into 25 functional networks. We have chosen top 2 functional networks, which comprised 10 miRNA (hsa-miR-516a-3p, hsa-miR-125b-1-3p, hsa-miR-221-5p, hsa-miR-7, hsa-miR-584-5p, hsa-miR-190a, hsa-miR-106a-5p, hsa-mir-376a-5p, hsa-mir-377-5p and hsa-let-7f-2-3p). Prediction of target mRNAs and associated biological pathways regulated by each of this miRNA was carried out. We paid special attention to hsa-miR-516a-3p and hsa-miR-7-5p as these miRNAs were highly expressed upon validation with qRT-PCR analysis. We further proceeded with loss-of-function analysis with these miRNAs and we observed that hsa-miR-516a-3p knockdown induced a significant increase in the expression of WNT5A. Likewise, the knockdown of hsa-miR-7-5p increased the expression of EGFR. Nevertheless, further validation revealed the role of WNT5A as an indirect target of hsa-miR-516a-3p. These results provide new insights into the dynamic role of miRNA expression in DPSCs. In conclusion, using miRNA signatures in human as a prediction tool will enable us to elucidate the biological processes occurring in DPSCs.
    Matched MeSH terms: MicroRNAs/genetics
  4. Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells
    Wong PF, Jamal J, Tong KL, Khor ES, Yeap CE, Jong HL, et al.
    Microvasc Res, 2017 11;114:26-33.
    PMID: 28595801 DOI: 10.1016/j.mvr.2017.06.002
    miRNAs are important regulators of cellular senescence yet the extent of their involvement remains to be investigated. We sought to identify miRNAs that are involved in cytokine-induced premature senescence (CIPS) in endothelial cells. CIPS was established in young human pulmonary microvascular endothelial cells (HMVEC-Ls) following treatment with a sublethal dose (20ng/ml) of tumor necrosis factor alpha (TNF-α) for 15days. In parallel, HMVEC-Ls were grown and routinely passaged until the onset of replicative senescence (RS). Differential expression analysis following miRNA microarray profiling revealed an overlapped of eight deregulated miRNAs in both the miRNA profiles of RS and TNF-α-induced premature senescence cells. Amongst the deregulated miRNAs were members of the miR 17-92 cluster which are known regulators of angiogenesis. The role of hsa-miR-20b in TNF-α-induced premature senescence, a paralog member of the miR 17-92 cluster, was further investigated. Biotin-labeled hsa-miR-20b captured the enriched transcripts of retinoblastoma-like 1 (RBL1), indicating that RBL1 is a target of hsa-miR-20b. Knockdown of hsa-miR-20b attenuated premature senescence in the TNF-α-treated HMVEC-Ls as evidenced by increased cell proliferation, increased RBL1 mRNA expression level but decreased protein expression of p16INK4a, a cellular senescence marker. These findings provide an early insight into the role of hsa-miR-20b in endothelial senescence.
    Matched MeSH terms: MicroRNAs/genetics
  5. World Workshop on Oral Medicine VII: Functional pathways involving differentially expressed lncRNAs in oral squamous cell carcinoma
    Pentenero M, Bowers L, Jayasinghe R, Cheong SC, Farah CS, Kerr AR, et al.
    Oral Dis, 2019 Jun;25 Suppl 1:79-87.
    PMID: 31140691 DOI: 10.1111/odi.13051
    Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.
    Matched MeSH terms: MicroRNAs/genetics*
  6. Fulltext Induction of Apoptosis and Regulation of MicroRNA Expression by (2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) Treatment on MCF-7 Breast Cancer Cells
    Yeap SK, Mohd Ali N, Akhtar MN, Razak NA, Chong ZX, Ho WY, et al.
    Molecules, 2021 Feb 26;26(5).
    PMID: 33652854 DOI: 10.3390/molecules26051277
    (2E,6E)-2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC) is a synthetic curcumin analogue, which has been reported to possess anti-tumor, anti-metastatic, and anti-invasion properties on estrogen receptor (ER) negative breast cancer cells in vitro and in vivo. However, the cytotoxic effects of BHMC on ER positive breast cancer cells were not widely reported. This study was aimed to investigate the cytotoxic potential of BHMC on MCF-7 cells using cell viability, cell cycle, and apoptotic assays. Besides, microarray and quantitative polymerase chain reaction (qPCR) were performed to identify the list of miRNAs and genes, which could be dysregulated following BHMC treatment. The current study discovered that BHMC exhibits selective cytotoxic effects on ER positive MCF-7 cells as compared to ER negative MDA-MB-231 cells and normal breast cells, MCF-10A. BHMC was shown to promote G2/M cell cycle arrest and apoptosis in MCF-7 cells. Microarray and qPCR analysis demonstrated that BHMC treatment would upregulate several miRNAs like miR-3195 and miR-30a-3p and downregulate miRNAs such as miR-6813-5p and miR-6132 in MCF-7 cells. Besides, BHMC administration was also found to downregulate few tumor-promoting genes like VEGF and SNAIL in MCF-7. In conclusion, BHMC induced apoptosis in the MCF-7 cells by altering the expressions of apoptotic-regulating miRNAs and associated genes.
    Matched MeSH terms: MicroRNAs/genetics*
  7. Fulltext Ectopic miR-975 induces CTP synthase directed cell proliferation and differentiation in Drosophila melanogaster
    Woo WK, Dzaki N, Thangadurai S, Azzam G
    Sci Rep, 2019 Apr 15;9(1):6096.
    PMID: 30988367 DOI: 10.1038/s41598-019-42369-6
    CTP synthase (CTPSyn) is an essential metabolic enzyme, synthesizing precursors required for nucleotides and phospholipids production. Previous studies have also shown that CTPSyn is elevated in various cancers. In many organisms, CTPSyn compartmentalizes into filaments called cytoophidia. In Drosophila melanogaster, only its isoform C (CTPSynIsoC) forms cytoophidia. In the fruit fly's testis, cytoophidia are normally seen in the transit amplification regions close to its apical tip, where the stem-cell niche is located, and development is at its most rapid. Here, we report that CTPSynIsoC overexpression causes the lengthening of cytoophidia throughout the entirety of the testicular body. A bulging apical tip is found in approximately 34% of males overexpressing CTPSynIsoC. Immunostaining shows that this bulged phenotype is most likely due to increased numbers of both germline cells and spermatocytes. Through a microRNA (miRNA) overexpression screen, we found that ectopic miR-975 concurrently increases both the expression levels of CTPSyn and the length of its cytoophidia. The bulging testes phenotype was also recovered at a penetration of approximately 20%. However, qPCR assays reveal that CTPSynIsoC and miR-975 overexpression each provokes a differential response in expression of a number of cancer-related genes, indicating that the shared CTPSyn upregulation seen in either case is likely the cause of observed testicular overgrowth. This study presents the first instance of consequences of miRNA-asserted regulation upon CTPSyn in D. melanogaster, and further reaffirms the enzyme's close ties to germline cells overgrowth.
    Matched MeSH terms: MicroRNAs/genetics*
  8. MicroRNA regulation of CTP synthase and cytoophidium in Drosophila melanogaster
    Dzaki N, Woo WK, Thangadurai S, Azzam G
    Exp Cell Res, 2019 12 15;385(2):111688.
    PMID: 31678212 DOI: 10.1016/j.yexcr.2019.111688
    CTPsyn is a crucial metabolic enzyme which synthesizes CTP nucleotides. It has the extraordinary ability to compartmentalize into filaments termed cytoophidia. Though the structure is evolutionarily conserved across kingdoms, the mechanisms behind their formation remain unknown. MicroRNAs (miRNAs) are short single-stranded RNA capable of directing mRNA silencing and degradation. D. melanogaster has a high total gene count to miRNA gene number ratio, alluding to the possibility that CTPsyn too may come under their regulation. A thorough miRNA overexpression involving 123 miRNAs was conducted, followed by CTPsyn-specific staining upon cytoophidia-rich egg chambers. This revealed a small group of candidates which confer either a lengthening or truncating effect on cytoophidia, suggesting they may play a role in regulating CTPsyn. MiR-975 and miR-1014 are both cytoophidia-elongating, whereas miR-190 and miR-932 are cytoophidia-shortening. Though target prediction shows that miR-975 and miR-932 do indeed have binding sites on CTPsyn mRNA, in vitro assays instead revealed a low probability of this being true, instead indicating that the effects asserted by overexpressed miRNAs indirectly reach CTPsyn and its cytoophidia through the actions of middling elements. In silico target prediction and qPCR quantification indicated that, at least for miR-932 and miR-1014, these undetermined elements may be players in fat metabolism. This is the first study to thoroughly investigate miRNAs in connection to CTPsyn expression and activity in any species. The findings presented could serve as a basis for further queries into not only the fundamental aspects of the enzyme's regulation, but may uncover new facets of closely related pathways as well.
    Matched MeSH terms: MicroRNAs/genetics
  9. PLASMA MICRORNA-133А LEVEL IN PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION
    Koval S, Snihurska I, Yushko K, Lytvynova O, Berezin A
    Georgian Med News, 2019 May.
    PMID: 31322515
    The aim of research was to investigate the plasma microRNA (miR-133а) level in patients with essential arterial hypertension (EAH). A total of 45 patients with EAH 2-3 degrees aged 52.14 ± 8.25 years and 21 healthy individuals (control group) with comparable age and sex distributions. The following frequency of risk factors was revealed among the examined patients: overweight (53%), dyslipidaemia (73%), pre-diabetes (13%), asymptomatic hyperuricemia (29%); hypertension-mediated organ damage: increased arterial stiffness (27%), left ventricular hypertrophy (55%), atherosclerotic plaque in the carotid artery (40%), microalbuminuria (15%), moderate stage of chronic kidney disease (22%) and cardiovascular diseases: stable ischemic heart disease (11%) and heart failure with preserved ejection fraction of NYHA functional class I (18%). The plasma miR-133a level was determined by polymerase chain reaction using "CFX96 Touch" detection system (BioRad) and "TaqMan microRNA Assay" and "TaqMan® Universal PCR Master Mix" reagents (Thermo Fisher Scientific, USA). It has been established that in patients with EAH the plasma level of miR-133a was significantly lower than in practically healthy individuals (0,182 [0,102; 0,301] ), vs (0,382 [0,198; 0,474]), p <0.05). It has also been revealed a significant decrease in the level of miR-133a in the blood plasma in patients with such organs damage as LVH (0,133 [0,099;0,184]) in comparison with patients without LVH (0,238 [0,155; 0,410]), p <0.05) and also significantly lower than in healthy subjects in the control group (0,382 [0,198; 0,474]), p<0.05). There were no statistically significant differences in the plasma levels of miR-133a in the group of patients with EAH, depending on the presence of risk factors, other organ damage and cardiovascular diseases. The findings suggest the significant role of reducing of plasma levels of miR-133a in the pathogenesis of hypertension itself and in pathological remodeling of the heart.
    Matched MeSH terms: MicroRNAs/genetics
  10. Deep parallel sequencing reveals conserved and novel miRNAs in gill and hepatopancreas of giant freshwater prawn
    Tan TT, Chen M, Harikrishna JA, Khairuddin N, Mohd Shamsudin MI, Zhang G, et al.
    Fish Shellfish Immunol, 2013 Oct;35(4):1061-9.
    PMID: 23816854 DOI: 10.1016/j.fsi.2013.06.017
    MicroRNAs (miRNAs) are ~20-22 nucleotides, non protein-coding RNA regulatory genes that post-transcriptionally regulate many protein-coding genes, influencing critical biological and metabolic processes. While the number of known microRNA is increasing, there is currently no published data for miRNA from giant freshwater prawns, Macrobrachium rosenbergii (M. rosenbergii), a commercially cultured and economically important food species. In this study, we identified novel miRNAs in the gill and hepatopancreas of M. rosenbergii. Through a deep parallel sequencing analysis and an in silico data analysis approach, 327 miRNA families were identified from small RNA libraries with reference to both the de novo transcriptome of M. rosenbergii obtained from RNA-Seq and to miRBase (Release 18.0, November 2012). Based on the identified mature miRNA and recovered precursor sequences that form appropriate hairpin structures, three conserved miRNA (miR125, miR750, miR993) and 27 novel miRNA candidates encoding messenger-like non-coding RNA were identified. miR-125, miR-750, G-m0002/H-m0009, G-m0005, G-m0008/H-m0016, G-m0011/H-m0027 and G-m0015 were selected for experimental validation with stem-loop quantitative RT-PCR and were found to be coherent with the expression profile of deep sequencing data as evaluated with Pearson's correlation coefficient (r = 0.835178 for miRNA in gill, r = 0.724131 for miRNA in hepatopancreas). Using a combinatorial approach of pathway enrichment analysis and inverse expression relationship of miRNA and mRNA, four co-expressed novel miRNA candidates (G-m0005, G-m0008/H-m0016, G-m0011/H-m0027, and G-m0015) were found to be associated with energy metabolism. In addition, the expression of the three novel miRNA candidates (G-m0005, G-m0008/H-m0016, and G-m0011/H-m0027) were also found to be significantly reduced at 9 and 24 h post infection in M. rosenbergii challenged with infectious hypodermal and hematopoietic necrosis virus, suggesting a functional role of these miRNAs in crustacean immune defense.
    Matched MeSH terms: MicroRNAs/genetics*
  11. Mixed-ligand copper(II) complex of quercetin regulate osteogenesis and angiogenesis
    Vimalraj S, Rajalakshmi S, Raj Preeth D, Vinoth Kumar S, Deepak T, Gopinath V, et al.
    Mater Sci Eng C Mater Biol Appl, 2018 Feb 01;83:187-194.
    PMID: 29208278 DOI: 10.1016/j.msec.2017.09.005
    Copper(II) complex of quercetin Cu+Q, mixed ligand complexes, quercetin-Cu(II)-phenanthroline [Cu+Q(PHt)] and quercetin-Cu(II)-neocuproine [Cu+Q(Neo)] have been synthesized and characterized. From the FT-IR spectroscopic studies, it was evident that C-ring of quercetin is involved in the metal chelation in all the three copper complexes. C-ring chelation was further proven by UV-Visible spectra and the presence of Cu(II) from EPR spectroscopic investigations. These complexes were found to have osteogenic and angiogenic properties, observed through in vitro osteoblast differentiation and chick embryo angiogenesis assay. In osteoblast differentiation, quercetin-Cu(II) complexes treatment increased calcium deposition and alkaline phosphatase activity (ALP) activity at the cellular level and stimulated Runx2 mRNA and protein, ALP mRNA and type 1 collagen mRNA expression at the molecular level. Among the complexes, Q+Cu(PHt) showed more effects on osteoblast differentiation when compared to that of other two copper complexes. Additionally, Q+Cu(Neo) showed more effect compared to Q+Cu. Furthermore, the effect of these complexes on osteoblast differentiation was confirmed by the expression of osteoblast specific microRNA, pre-mir-15b. The chick embryo angiogenesis assay showed that angiogenic parameters such as blood vessel length, size and junctions were stimulated by these complexes. Thus, the present study demonstrated that quercetin copper(II) complexes exhibit as a pharmacological agent for the orthopedic application.
    Matched MeSH terms: MicroRNAs/genetics
  12. The Potential Role of miRNAs as Predictive Biomarkers in Neurodevelopmental Disorders
    Juvale IIA, Che Has AT
    J Mol Neurosci, 2021 Jul;71(7):1338-1355.
    PMID: 33774758 DOI: 10.1007/s12031-021-01825-7
    Neurodevelopmental disorders are defined as a set of abnormal brain developmental conditions marked by the early childhood onset of cognitive, behavioral, and functional deficits leading to memory and learning problems, emotional instability, and impulsivity. Autism spectrum disorder, attention-deficit/hyperactivity disorder, Tourette syndrome, fragile X syndrome, and Down's syndrome are a few known examples of neurodevelopmental disorders. Although they are relatively common in both developed and developing countries, very little is currently known about their underlying molecular mechanisms. Both genetic and environmental factors are known to increase the risk of neurodevelopmental disorders. Current diagnostic and screening tests for neurodevelopmental disorders are not reliable; hence, individuals with neurodevelopmental disorders are often diagnosed in the later stages. This negatively affects their prognosis and quality of life, prompting the need for a better diagnostic biomarker. Recent studies on microRNAs and their altered regulation in diseases have shed some light on the possible role they could play in the development of the central nervous system. This review attempts to elucidate our current understanding of the role that microRNAs play in neurodevelopmental disorders with the hope of utilizing them as potential biomarkers in the future.
    Matched MeSH terms: MicroRNAs/genetics
  13. Fulltext The Interplay between MicroRNAs and Cellular Components of Tumour Microenvironment (TME) on Non-Small-Cell Lung Cancer (NSCLC) Progression
    Lee SS, Cheah YK
    J Immunol Res, 2019;2019:3046379.
    PMID: 30944831 DOI: 10.1155/2019/3046379
    Cellular components of the tumour microenvironment (TME) are recognized to regulate the hallmarks of cancers including tumour proliferation, angiogenesis, invasion, and metastasis, as well as chemotherapeutic resistance. The linkage between miRNA, TME, and the development of the hallmarks of cancer makes miRNA-mediated regulation of TME a potential therapeutic strategy to complement current cancer therapies. Despite significant advances in cancer therapy, lung cancer remains the deadliest form of cancer among males in the world and has overtaken breast cancer as the most fatal cancer among females in more developed countries. Therefore, there is an urgent need to develop more effective treatments for NSCLC, which is the most common type of lung cancer. Hence, this review will focus on current literature pertaining to antitumour or protumourigenic effects elicited by nonmalignant stromal cells of TME in NSCLC through miRNA regulation as well as current status and future prospects of miRNAs as therapeutic agents or targets to regulate TME in NSCLC.
    Matched MeSH terms: MicroRNAs/genetics*
  14. microRNAs expression profiles in Schistosoma japonicum of different sex 14 and 28 days post-infection
    Ai L, Hu W, Zhang RL, Huang DN, Chen SH, Xu B, et al.
    Trop Biomed, 2020 Dec 01;37(4):947-962.
    PMID: 33612748 DOI: 10.47665/tb.37.4.947
    Different miRNAs are involved in the life cycles of Schistosoma japonicum. The aim of this study was to examine the expression profile of miRNAs in individual S. japonicum of different sex before and after pairing (18 and 24 dpi). The majority of differential expressed miRNAs were highly abundant at 14 dpi, except for sja-miR-125b and sja-miR-3505, in both male and female. Moreover, it was estimated that sja-miR-125b and sja-miR-3505 might be related to laying eggs. sja-miR-2a-5p and sja-miR-3484-5p were expressed at 14 dpi in males and were significantly clustered in DNA topoisomerase III, Rap guanine nucleotide exchange factor 1 and L-serine/L-threonine ammonia-lyase. Target genes of sja-miR-2d-5p, sja-miR-31- 5p and sja-miR-125a, which were expressed at 14 dpi in males but particularly females, were clustered in kelch-like protein 12, fructose-bisphosphate aldolase, class I, and heat shock protein 90 kDa beta. Predicted target genes of sja-miR-3483-3p (expressed at 28 dpi in females but not in males) were clustered in 26S proteasome regulatory subunit N1, ATPdependent RNA helicase DDX17. Predicted target genes of sja-miR-219-5p, which were differentially expressed at 28 dpi in females but particularly males, were clustered in DNA excision repair protein ERCC-6, protein phosphatase 1D, and ATPase family AAA domaincontaining protein 3A/B. Moreover, at 28 dpi, eight miRNAs were significantly up-regulated in females compared to males. The predicted target genes of these miRNAs were significantly clustered in heat shock protein 90 kDa beta, 26S proteasome regulatory subunit N1, and protein arginine N-methyltransferase 1. To sum up, differentially expressed miRNAs may have an essential role and provide necessary information on clarifying this trematode's growth, development, maturation, and infection ability to mammalian hosts in its complex life cycle, and may be helpful for developing new drug targets and vaccine candidates for schistosomiasis.
    Matched MeSH terms: MicroRNAs/genetics*
  15. Fulltext Mapping a Circular RNA-microRNA-mRNA-Signaling Regulatory Axis That Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells
    Rengganaten V, Huang CJ, Tsai PH, Wang ML, Yang YP, Lan YT, et al.
    Int J Mol Sci, 2020 Oct 23;21(21).
    PMID: 33114016 DOI: 10.3390/ijms21217864
    Spheroidal cancer cell cultures have been used to enrich cancer stem cells (CSC), which are thought to contribute to important clinical features of tumors. This study aimed to map the regulatory networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal cancer (CRC) spheroid cells. The spheroid cells established from two CRC cell lines acquired stemness properties in pluripotency gene expression and multi-lineage differentiation capacity. Genome-wide sequencing identified 1503 and 636 circRNAs specific to the CRC parental and spheroid cells, respectively. In the CRC spheroids, algorithmic analyses unveiled a core network of mRNAs involved in modulating stemness-associated signaling pathways, driven by a circRNA-microRNA (miRNA)-mRNA axis. The two major circRNAs, hsa_circ_0066631 and hsa_circ_0082096, in this network were significantly up-regulated in expression levels in the spheroid cells. The two circRNAs were predicted to target and were experimentally shown to down-regulate miR-140-3p, miR-224, miR-382, miR-548c-3p and miR-579, confirming circRNA sponging of the targeted miRNAs. Furthermore, the affected miRNAs were demonstrated to inhibit degradation of six mRNA targets, viz. ACVR1C/ALK7, FZD3, IL6ST/GP130, SKIL/SNON, SMAD2 and WNT5, in the CRC spheroid cells. These mRNAs encode proteins that are reported to variously regulate the GP130/Stat, Activin/Nodal, TGF-β/SMAD or Wnt/β-catenin signaling pathways in controlling various aspects of CSC stemness. Using the CRC spheroid cell model, the novel circRNA-miRNA-mRNA axis mapped in this work forms the foundation for the elucidation of the molecular mechanisms of the complex cellular and biochemical processes that determine CSC stemness properties of cancer cells, and possibly for designing therapeutic strategies for CRC treatment by targeting CSC.
    Matched MeSH terms: MicroRNAs/genetics*
  16. 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: MicroRNAs/genetics
  17. Fulltext Role of microRNAs in Diagnosis, Prognosis and Management of Multiple Myeloma
    Soliman AM, Lin TS, Mahakkanukrauh P, Das S
    Int J Mol Sci, 2020 Oct 13;21(20).
    PMID: 33066062 DOI: 10.3390/ijms21207539
    Multiple myeloma (MM) is a cancerous bone disease characterized by malignant transformation of plasma cells in the bone marrow. MM is considered to be the second most common blood malignancy, with 20,000 new cases reported every year in the USA. Extensive research is currently enduring to validate diagnostic and therapeutic means to manage MM. microRNAs (miRNAs) were shown to be dysregulated in MM cases and to have a potential role in either progression or suppression of MM. Therefore, researchers investigated miRNAs levels in MM plasma cells and created tools to test their impact on tumor growth. In the present review, we discuss the most recently discovered miRNAs and their regulation in MM. Furthermore, we emphasized utilizing miRNAs as potential targets in the diagnosis, prognosis and treatment of MM, which can be useful for future clinical management.
    Matched MeSH terms: MicroRNAs/genetics*
  18. Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment
    Teoh SL, Das S
    Tumour Biol., 2016 Nov;37(11):14363-14380.
    PMID: 27623943
    Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.
    Matched MeSH terms: MicroRNAs/genetics
  19. The Role of MicroRNAs in Diagnosis, Prognosis, Metastasis and Resistant Cases in Breast Cancer
    Teoh SL, Das S
    Curr Pharm Des, 2017;23(12):1845-1859.
    PMID: 28231756 DOI: 10.2174/1381612822666161027120043
    The incidence and mortality due to breast cancer is increasing worldwide. There is a constant quest to know the underlying molecular biology of breast cancer in order to arrive at diagnosis and plan better treatment options. MicroRNAs (miRNAs) are small non-coding and single stranded RNAs which influence the gene expression and physiological condition in any tumor. The miRNAs may act on different pathways in various cancers. Recently, there are research reports on various miRNAs being linked to breast cancers. The important miRNAs associated with breast cancers include miR-21, miR-155, miR-27a, miR-205, miR-145 and miR-320a. In the present review we discuss the role of miRNAs in breast cancer, its importance as diagnostic markers, prognosis and metastasis markers. We also highlight the role of miRNAs with regard to resistance to few anticancerous drugs such as Tamoxifen and Trastuzumab. The role of miRNA in resistance to treatment is one of the core issues discussed in the present review. Much information on the miRNA roles is available particularly in the neoadjuvant chemotherapy setting, because this protocol allows the rapid association of miRNA expression with the treatment response. This review opens the door for designing better therapeutic options in drug resistance cases in breast cancer.
    Matched MeSH terms: MicroRNAs/genetics*
  20. Fulltext IsomiRs have functional importance
    Tan GC, Dibb N
    Malays J Pathol, 2015 Aug;37(2):73-81.
    PMID: 26277662 MyJurnal
    Since the inception of deep sequencing, isomiRs are consistently observed to be produced by most miRNA genes in a variety of cell types. IsomiRs appear as a variation in length from the canonical sequence annotated in miRBase, due to an addition or deletion of one or more nucleotides at the 5(') or 3(') ends or both. As the seed sequence is located at the 5(') end of the microRNA, the target mRNA will be theoretically different. Therefore, 5(')isomiRs might potentially target a new set mRNA compared to their canonical counterpart. This article gives an overview of investigations that explored the functional potential of isomiRs such as their ability to incorporate into Argonaute protein, the differential expression of isomiRs in various tissue types and cell lines, and the differences of mRNA targets between isomiR and its canonical microRNA. In addition, this article provides a brief introduction of RNA sponges as a potential way to inhibit isomiRs.
    Matched MeSH terms: MicroRNAs/genetics*
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