Displaying publications 1 - 20 of 285 in total

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  1. Chai AWY, Yee PS, Price S, Yee SM, Lee HM, Tiong VK, et al.
    Elife, 2020 09 29;9.
    PMID: 32990596 DOI: 10.7554/eLife.57761
    New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identified OSCC-related cancer genes are non-essential and could have limited therapeutic value, while other fitness genes warrant further investigation for their potential as therapeutic targets. We validate a distinctive dependency on YAP1 and WWTR1 of the Hippo pathway, where the lost-of-fitness effect of one paralog can be compensated only in a subset of lines. We also discover that OSCCs with WWTR1 dependency signature are significantly associated with biomarkers of favorable response toward immunotherapy. In summary, we have delineated the genetic vulnerabilities of OSCC, enabling the prioritization of therapeutic targets for further exploration, including the targeting of YAP1 and WWTR1.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  2. Gam LH, Leow CH, Man CN, Gooi BH, Singh M
    World J Gastroenterol, 2006 Aug 21;12(31):4973-80.
    PMID: 16937492
    AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.

    METHODS: Colon tissues (normal and cancerous) were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.

    RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.

    CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  3. Tan BL, Norhaizan ME, Huynh K, Yeap SK, Hazilawati H, Roselina K
    World J Gastroenterol, 2015 Aug 7;21(29):8826-35.
    PMID: 26269672 DOI: 10.3748/wjg.v21.i29.8826
    To investigate the mechanistic action of brewers' rice in regulating the Wnt/nuclear factor-kappa B (NF-κB)/Nrf2-signaling pathways during colon carcinogenesis in male Sprague-Dawley rats.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  4. Ali Y, Abd Hamid S
    Tumour Biol., 2016 Jan;37(1):47-55.
    PMID: 26482620 DOI: 10.1007/s13277-015-4270-9
    Topoisomerases are nuclear enzymes that regulate topology of DNA by facilitating the temporary cleavage and ligation cycle of DNA. Among all forms of topoisomerases, TOP-IIA is extensively associated with cell proliferation and therefore is an important therapeutic target in diseases that involved cellular proliferation such as cancers. Nearly half of present-day antitumor regimens contain at least one prescription that act as a topoisomerase inhibitor. Generally, tumor cells show divergent expression of TOP-IIA compared to normal cells. The remarkable expression of TOP-IIA in various carcinomas provides a significant biomarker toward understanding the nature of malignancy. TOP-IIA expression and amplification studies help in diagnosing cancer and to observe the disease progression, overall survival (OS) of patients, and response to therapy. This review highlights the research output and analysis in exploring the standing of TOP-IIA in various carcinomas. As some reports show contradiction within the same field of interest, the outline of that may help to induce researchers for further investigation and clarification. To the best of our knowledge, this is the first overview briefly summarizing the prognostic feature of TOP-IIA in various types of cancer.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  5. Goh KW, Say YH
    Tumour Biol., 2015 Sep;36(10):7947-60.
    PMID: 25956278 DOI: 10.1007/s13277-015-3455-6
    γ-synuclein, a neuronal protein of the synuclein family, is involved in carcinogenesis. To investigate its role in colorectal cancer carcinogenesis, we overexpressed γ-synuclein in LS 174T colon adenocarcinoma cell line (termed LS 174T-γsyn). When compared with untransfected/mock transfectants, LS 174T-γsyn had higher mobility in scratch wound assay, tend to scatter more in cell-scattering assay, and had enhanced lamellipodia and filopodia formation in cell-spreading assay. Enhanced adhesion of LS 174T-γsyn to fibronectin and collagen and significantly higher proliferation rate showed that γ-synuclein was able to increase extracellular matrix interaction and promoted proliferation of LS 174T. Higher invasiveness of LS 174T-γsyn was evidenced by enhanced invasion to the bottom of the basement membrane in Boyden chamber assay. However, LS 174T-γsyn were significantly more vulnerable to doxorubicin, vincristine and hydrogen peroxide insults, via apoptotic cell death. LS 174T-γsyn also had reduced anchorage-independent growth as shown by reduced colony formation and reduced anoikis resistance. We found that overexpression of γ-synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to LS 174T, where the former was mediated through enhanced cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation, while the latter involved hepatocyte growth factor (HGF) downregulation and subsequent downstream signalling pathways possibly involving extracellular signal-regulated kinases (ERK)1/2, p38α, c-Jun N-terminal kinase (JNK) pan and Signal Transducers and Activators of Transcription (STATs). This unexpected contrasting finding as compared to other similar studies on colon cancer cell lines might be correlated with the degree of tumour advancement from which the cell lines were derived from.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*
  6. Omer FAA, Hashim NBM, Ibrahim MY, Dehghan F, Yahayu M, Karimian H, et al.
    Tumour Biol., 2017 Nov;39(11):1010428317731451.
    PMID: 29110583 DOI: 10.1177/1010428317731451
    Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G0/G1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G0/G1 phase and prompted the intrinsic apoptosis pathway.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  7. Ma XR, Edmund Sim UH, Pauline B, Patricia L, Rahman J
    Trop Biomed, 2008 Apr;25(1):46-57.
    PMID: 18600204 MyJurnal
    Colorectal carcinoma (CRC) arises as a result of mutational activation of oncogenes coupled with inactivation of tumour suppressor genes. Mutations in APC, K-ras and p53 have been commonly reported. In a previous study by our group, the tumour susceptibility gene 101 (TSG101) were found to be persistently upregulated in CRC cases. TSG101 was reported to be closely related to cancers of the breast, brain and colon, and its overexpression in human papillary thyroid carcinomas and ovarian carcinomas had previously been reported. The wingless-type MMTV integration site family member 2 (WNT2) is potentially important in the Wnt/beta-catenin pathway and upregulation of WNT2 is not uncommon in human cancers. In this study, we report the investigation for mutation(s) and expression pattern(s) of WNT2 and TSG101, in an effort to further understand their role(s) in CRC tumourigenesis. Our results revealed no mutation in these genes, despite their persistent upregulation in CRC cases studied.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  8. Ng WK, Yazan LS, Ismail M
    Toxicol In Vitro, 2011 Oct;25(7):1392-8.
    PMID: 21609759 DOI: 10.1016/j.tiv.2011.04.030
    Thymoquinone (TQ), the active constituent of Nigella sativa or black cumin exhibited cytotoxic effects in several cancer cell lines. In this study, the cytotoxicity of TQ in human cervical squamous carcinoma cells (SiHa) was investigated. TQ was cytotoxic towards SiHa cells with IC50 values of 10.67 ± 0.12 and 9.33 ± 0.19 μg/mL as determined by MTT assay and trypan blue dye exclusion test, respectively, after 72 h of incubation. TQ was more cytotoxic towards SiHa cells compared to cisplatin. Interestingly, TQ was less cytotoxic towards the normal cells (3T3-L1 and Vero). Cell cycle analysis performed by flowcytometer showed a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Apoptosis induction by TQ was further confirmed by Annexin V/PI and AO/PI staining. Significant elevation of p53 and down-regulation of the anti-apoptotic Bcl-2 protein was found in the treated cells, without any changes in the expression of the pro-apoptotic Bax protein. In conclusion, thymoquinone from N. sativa was more potent than cisplatin in elimination of SiHa cells via apoptosis with down-regulation of Bcl-2 protein.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  9. Quah SY, Wong CC, Wong HC, Ho KL, Abdul Manan N, Deb PK, et al.
    Toxicol Appl Pharmacol, 2021 08 15;425:115605.
    PMID: 34087331 DOI: 10.1016/j.taap.2021.115605
    Chemoresistance poses a major hurdle to cancer treatments. Andrographolide-derived SRJ09 and SRJ23 were reported to exhibit potent, selective inhibitory activities against colon and prostate cancer cells, respectively. In this study, previously developed resistant colon (HCT-116rst09) and prostate (PC-3rst23) cancer cell lines were used to elucidate the molecular mechanisms contributing to chemoresistance. Cytotoxic effects of SRJ09 and SRJ23 on both parental and resistant cells were investigated. Cell cycle distributions in HCT-116rst09 cells following SRJ09 treatment were analysed using flow cytometry. Whole-genome microarray analysis was performed on both parental and resistant cells to obtain differential gene expression profiles. Microarray data were subjected to protein-protein interaction network, functional enrichment, and pathway analyses. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the changes in expression levels of selected genes. Besides morphological changes, HCT-116rst09 cells showed 7.0-fold resistance to SRJ09 while PC-3rst23 cells displayed a 5.5-fold resistance to SRJ23, as compared with their respective parental cells. G0/G1-phase cell cycle arrest was observed in HCT-116rst09 cells upon SRJ09 treatment. Collectively, 77 and 21 genes were found differentially modulated in HCT-116rst09 and PC-3rst23 cells, respectively. Subsequent bioinformatics analysis revealed several genes associated with FGFR4 and PI3K pathways, and cancer stemness, were chemoresistance mediators in HCT-116rst09 cells. RT-PCR confirmed the HMOX1 upregulation and ATG12 downregulation protected the PC-3rst23 cells from SRJ23 cytotoxicity. In conclusion, acquired chemoresistance to SRJ09 and SRJ23 in colon and prostate cancer cells, respectively, could be attributed to the alterations in the expression of genes such as those related to PI3K and autophagy pathways.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  10. Nesaretnam K, Jin Lim E, Reimann K, Lai LC
    Toxicology, 2000 Oct 26;151(1-3):117-26.
    PMID: 11074306
    Breast cancer is the most common cancer in women worldwide. The growth of breast cancer cells is either hormone-dependent or hormone-independent. Both types are represented in vitro by the estrogen-receptor positive (ER+) MCF-7 and the estrogen-receptor negative (ER-) MDA-MB-231 cell lines, respectively. The pS2 gene is an estrogen-regulated gene and serves as a marker for the ER+ tumours. Carotenoids are pigments with anti-cancer properties besides having pro-vitamin A, antioxidant and free-radical quenching effects. This study was designed firstly, to compare the effect of palm oil carotene concentrate with retinoic acid on the growth of the ER+ MCF-7 and the ER- MDA-MB-231 cells; and secondly to evaluate the effect of the palm oil carotene concentrate on the regulation of pS2 mRNA. The growth experiments were performed with monolayer cells seeded in phenol red free RPMI 1640 culture media and subsequently treated with varying concentrations of either retinoic acid or palm oil carotenoids. The cell numbers were determined at the start of each experiment and then at successive time intervals. The results showed that the palm oil carotene concentrate caused dose-dependent inhibition of estradiol-stimulated growth of MCF-7 cells but did not affect the proliferation of MDA-MB-231 cells. Retinoic acid caused similar, albeit more potent effects, as significant inhibition was observed at lower concentrations than the palm oil carotenoids. In the pS2 gene expression experiment, cell monolayers were treated with the carotene concentrate (10(-6) M), either with or without supplemented estradiol (10(-8) M), and subsequently the RNA was extracted. Northern blotting was performed and the regulation of pS2 mRNA determined using a 32P-labelled pS2 cDNA probe. The results showed that the palm oil carotene concentrate did not affect the expression of pS2 mRNA and are therefore independent of the estrogen-regulated pathway.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*; Gene Expression Regulation, Neoplastic/genetics
  11. Zhou X, Li Y, Wang W, Wang S, Hou J, Zhang A, et al.
    Theranostics, 2020;10(21):9443-9457.
    PMID: 32863938 DOI: 10.7150/thno.46078
    Objective: Esophageal squamous cell carcinoma (ESCC) is one of the most commonly diagnosed cancer types in China. Recent genomic sequencing analysis indicated the over-activation of Hippo/YAP signaling might play important roles for the carcinogenic process and progression for ESCC patients. However, little is known about the molecular mechanisms that controls Hippo signaling activity in ESCC. Our previous studies indicated that PLCE1-an important risk factor for ESCC-linked to ESCC progression through snail signaling, during this period, we found PARK2 was an important downstream target of PLCE1-snail axis. PARK2 was decreased in ESCC human samples, and correlated with good prognosis in ESCC patients. Further research showed that PARK2 could inhibit YAP, which functions as key downstream effectors of the Hippo pathway. Here, we aim to reveal the molecular mechanisms of PARK2 modulated Hippo pathway in ESCC. Methods: To evaluate the function of PARK2 in ESCC, we used a tissue microarray (TMA) of 223 human ESCC patients and immunohistochemistry to analyze the correlation between PARK2 expression and clinicopathologic variables. Depletion of endogenous PARK2 and YAP from ESCC cells using CRISPR/Cas9 technologies. Flow cytometry and EdU cell proliferation assay were used to detect proliferation of ESCC cells. Nude mice subcutaneous injection and Ki-67 staining were used to evaluate tumor growth in vivo. Migration and invasion assays were performed. In addition, lung metastasis models in mice were used to validate the function of PARK2 in vivo. Identification of PARK2 involved in hippo pathway was achieved by expression microarray screening, double immunofluorescence staining and co-immunoprecipitation assays. The RNA-seq analysis results were validated through quantitative real-time PCR (qRT-PCR) analysis. The protein half-life of YAP was analyzed by Cycloheximide assay, and the TEAD activity was detected by Luciferase reporter assays. Results: Clinical sample of ESCC revealed that low PARK2 expression correlated with late tumor stage (P < 0.001), poor differentiation (P < 0.04), lymph node (P < 0.001) and distant metastasis (P = 0.0087). Multivariate Cox proportional regression analysis further revealed that PARK2 expression (P = 0.032) is an independent prognostic factor for the overall survival of ESCC patients. Besides, the immunohistochemistry results showed that PARK2 negatively correlated with YAP protein level (P < 0.001). PARK2 depletion promotes ESCC progression both through Hippo/YAP axis, while PARK2 overexpression suppresses ESCC tumor progression by Hippo signaling. Co-IP and ubiquitination assays revealed that PARK2 could interact with YAP in the cytosol and promotes YAP K48-linked ubiquitination at K90 sites. Conclusion: Clinical sample analysis and mechanistic study have validated PARK2 as a tumor suppressor for ESCC. Multivariate Cox proportional regression analysis further revealed that PARK2 is an independent prognostic factor for the overall survival of ESCC patients. Cellular and molecular mechanisms in this study showed that PARK2 associated with YAP protein in the cytosol, promoted YAP ubiquitination and proteasome-dependent degradation in ESCC cells. Therefore, as a novel modulator for Hippo signaling, modulation of PARK2 activity or gene expression level could be an appealing strategy to treat esophageal.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/genetics
  12. Vincent-Chong VK, Salahshourifar I, Karen-Ng LP, Siow MY, Kallarakkal TG, Ramanathan A, et al.
    ScientificWorldJournal, 2014;2014:897523.
    PMID: 25401159 DOI: 10.1155/2014/897523
    Matrix metalloproteinase 13 (MMP13) plays a central role in the MMP activation cascade that enables degradation of the extracellular matrix and basement membranes, and it is identified as a potential driver in oral carcinogenesis. Therefore, this study aims to determine the copy number, mRNA, and protein expression of MMP13 in oral squamous cell carcinoma (OSCC) and to associate these expressions with clinicopathological parameters. Copy number, mRNA, and protein expression analysis of MMP13 were determined using real-time quantitative PCR and immunohistochemistry methods in OSCC samples. The correlations between MMP13 expressions and clinicopathological parameters were evaluated, and the significance of MMP13 as a prognostic factor was determined. Despite discrepancies between gene amplification and mRNA and protein overexpression rates, OSCC cases showed high amplification of MMP13 and overexpression of MMP13 at both mRNA and protein levels. High level of MMP13 protein expression showed a significant correlation with lymph node metastasis (P = 0.011) and tumor staging (P = 0.002). Multivariate Cox regression model analysis revealed that high level of mRNA and protein expression of MMP13 were significantly associated with poor prognosis (P < 0.050). Taken together, these observations indicate that the MMP13 protein overexpression could be considered as a prognostic marker of OSCC.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  13. Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  14. Aravind SR, Joseph MM, George SK, Dileep KV, Varghese S, Rose-James A, et al.
    Int J Biochem Cell Biol, 2015 Feb;59:153-66.
    PMID: 25541375 DOI: 10.1016/j.biocel.2014.11.019
    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive target for cancer therapy due to its ability to selectively induce apoptosis in cancer cells, without causing significant toxicity in normal tissues. We previously reported that galactoxyloglucan (PST001) possesses significant antitumor and immunomodulatory properties. However, the exact mechanism in mediating this anticancer effect is unknown. This study, for the first time, indicated that PST001 sensitizes non-small cell lung cancer (A549) and nasopharyngeal (KB) cells to TRAIL-mediated apoptosis. In vitro studies suggested that PST001 induced apoptosis primarily via death receptors and predominantly activated caspases belonging to the extrinsic apoptotic cascade. Microarray profiling of PST001 treated A549 and KB cells showed the suppression of survivin (BIRC5) and anti-apoptotic Bcl-2, as well as increased cytochrome C. TaqMan low density array analysis of A549 cells also confirmed that the induction of apoptosis by the polysaccharide occurred through the TRAIL-DR4/DR5 pathways. This was finally confirmed by in silico analysis, which revealed that PST001 binds to TRAIL-DR4/DR5 complexes more strongly than TNF and Fas ligand-receptor complexes. In summary, our results suggest the potential of PST001 to be developed as an anticancer agent that not only preserves innate biological activity of TRAIL, but also sensitizes cancer cells to TRAIL-mediated apoptosis.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  15. Hung TH, Chen CM, Tseng CP, Shen CJ, Wang HL, Choo KB, et al.
    Int J Biochem Cell Biol, 2014 Aug;53:55-65.
    PMID: 24814288 DOI: 10.1016/j.biocel.2014.04.011
    Multidrug-resistant (MDR) cancer is a major clinical problem in chemotherapy of cancer patients. We have noted inappropriate PKCδ hypomethylation and overexpression of genes in the PKCδ/AP-1 pathway in the human uterus sarcoma drug-resistant cell line, MES-SA/Dx5 cells, which also overexpress p-glycoprotein (ABCB1). Recent studies have indicated that FZD1 is overexpressed in both multidrug-resistant cancer cell lines and in clinical tumor samples. These data have led us to hypothesize that the FZD1-mediated PKCδ signal-transduction pathway may play an important role in drug resistance in MES-SA/Dx5 cells. In this work, the PKCδ inhibitor Rottlerin was found to reduce ABCB1 expression and to inhibit the MDR drug pumping ability in the MES-SA/Dx5 cells when compared with the doxorubicin-sensitive parental cell line, MES-SA. PKCδ was up-regulated with concurrent up-regulation of the mRNA levels of the AP-1-related factors, c-JUN and c-FOS. Activation of AP-1 also correlated with up-regulation of the AP-1 downstream genes HGF and EGR1. Furthermore, AP-1 activities were reduced and the AP-1 downstream genes were down-regulated in Rottlerin-treated or PKCδ shRNA-transfected cells. MES-SA/Dx5 cells were resensitized to doxorubicin-induced toxicity by co-treatment with doxorubicin and Rottlerin or PKCδ shRNA. In addition, cell viability and drug pump-out ability were significantly reduced in the FZD1 inhibitor curcumin-treated and FZD1 shRNA-knockdown MES-SA/Dx5 cells, indicating involvement of PKCδ in FZD1-modulated ABCB1 expression pathway. Taken together, our data demonstrate that FZD1 regulates PKCδ, and the PKCδ/AP-1 signalling transduction pathway plays an important role in drug resistance in MES-SA/Dx5 cells.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  16. Chew CH, Chew GS, Najimudin N, Tengku-Muhammad TS
    Int J Biochem Cell Biol, 2007;39(10):1975-86.
    PMID: 17616429
    Peroxisome proliferator activated receptor alpha has been implicated as a regulator of acute phase response genes in hepatocytes. Interleukin-6 is widely known as a major cytokine responsible in the regulation of acute phase proteins and, therefore, acute phase response. Unfortunately, to date, very little is understood about the molecular mechanisms by which interleukin-6 regulates the gene expression of peroxisome proliferator activated receptor alpha. Here, we report the molecular mechanisms by which peroxisome proliferator activated receptor alpha was regulated by interleukin-6 in human HepG2 cells. Interleukin-6 was shown to down-regulate the peroxisome proliferator activated receptor alpha gene expression at the level of gene transcription. Functional dissection of human peroxisome proliferator activated receptor alpha promoter B revealed the role of predicted CCAAT/enhancer-binding protein binding site (-164/+34) in mediating the interleukin-6 inhibitory effects on peroxisome proliferator activated receptor alpha mRNA expression and electrophoretic mobility shift assay showed the binding of CCAAT/enhancer-binding protein isoforms to this cis-acting elements was increased in interleukin-6-treated HepG2 cells. Co-transfection experiments, then, demonstrated that CCAAT/enhancer-binding protein beta either in homodimer or heterodimer with CCAAT/enhancer-binding protein alpha and CCAAT/enhancer-binding protein delta plays a predominant role in inhibiting the transcriptional activity of peroxisome proliferator activated receptor alpha promoter B, thus, reducing the peroxisome proliferator activated receptor alpha mRNA expression. These studies, therefore, suggest a novel mechanism for interleukin-6-mediated inhibition of peroxisome proliferator activated receptor alpha gene expression that involves the activation of CCAAT/enhancer-binding protein isoforms with CCAAT/enhancer-binding protein beta may play a major role.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
  17. Veerasamy T, Eugin Simon S, Tan KO
    Int J Biochem Cell Biol, 2021 08;137:106016.
    PMID: 34082133 DOI: 10.1016/j.biocel.2021.106016
    Conventional chemotherapy relies on the cytotoxicity of chemo-drugs to inflict destructive effects on tumor cells. However, as most tumor cells develop resistance to chemo-drugs, small doses of chemo-drugs are unlikely to provide significant clinical benefits in cancer treatment while high doses of chemo-drugs have been shown to impact normal human cells negatively due to the non-specific nature and cytotoxicity associated with chemo-drugs. To overcome this challenge, sensitizations of tumor cells with bioactive molecules that specifically target the pro-survival and pro-apoptosis signaling pathways of the tumor cells are likely to increase the therapeutic impacts and improve the clinical outcomes by reducing the dependency and adverse effects associated with using high doses of chemo-drugs in cancer treatment. This review focuses on emerging strategies to enhance the sensitization of tumor cells toward cancer therapies based on our understanding of tumor cell biology and underlying signaling pathways.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*
  18. Hor YZ, Salvamani S, Gunasekaran B, Yian KR
    Yale J Biol Med, 2023 Dec;96(4):511-526.
    PMID: 38161583 DOI: 10.59249/VHYE2306
    Colorectal Neoplasia Differentially Expressed (CRNDE), a long non-coding RNA that was initially identified as aberrantly expressed in colorectal cancer (CRC) has also been observed to exhibit elevated expression in various other human malignancies. Recent research has accumulated substantial evidence implicating CRNDE as an oncogenic player, exerting influence over critical cellular processes linked to cancer progression. Particularly, its regulatory interactions with microRNAs and proteins have been shown to modulate pathways that contribute to carcinogenesis and tumorigenesis. This review will comprehensively outline the roles of CRNDE in colorectal, liver, glioma, lung, cervical, gastric and prostate cancer, elucidating the mechanisms involved in modulating proliferation, apoptosis, migration, invasion, angiogenesis, and radio/chemoresistance. Furthermore, the review highlights CRNDE's potential as a multifaceted biomarker, owing to its presence in diverse biological samples and stable properties, thereby underscoring its diagnostic, therapeutic, and prognostic applications. This review aims to provide comprehensive insights of CRNDE-mediated oncogenesis and identify CRNDE as a promising target for future clinical interventions.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/genetics
  19. Chowdhury PR, Salvamani S, Gunasekaran B, Peng HB, Ulaganathan V
    Yale J Biol Med, 2023 Dec;96(4):495-509.
    PMID: 38161577 DOI: 10.59249/TDBJ7410
    Colorectal cancer (CRC) has been recorded amongst the most common cancers in the world, with high morbidity and mortality rates, and relatively low survival rates. With risk factors such as chronic illness, age, and lifestyle associated with the development of CRC, the incidence of CRC is increasing each year. Thus, the discovery of novel biomarkers to improve the diagnosis and prognosis of CRC has become beneficial. Long non-coding RNAs (lncRNAs) have been emerging as potential players in several tumor types, one among them is the lncRNA H19. The paternally imprinted oncofetal gene is expressed in the embryo, downregulated at birth, and reappears in tumors. H19 aids in CRC cell growth, proliferation, invasion, and metastasis via various mechanisms of action, significantly through the lncRNA-microRNA (miRNA)-messenger RNA (mRNA)-competitive endogenous RNA (ceRNA) network, where H19 behaves as a miRNA sponge. The RNA transcript of H19 obtained from the first exon of the H19 gene, miRNA-675 also promotes CRC carcinogenesis. Overexpression of H19 in malignant tissues compared to adjacent non-malignant tissues marks H19 as an independent prognostic marker in CRC. Besides its prognostic value, H19 serves as a promising target for therapy in CRC treatment.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/genetics
  20. Hashim M, Tizen NMS, Alfian N, Hashim H, Nawi AM, Pauzi SHM
    Pan Afr Med J, 2021;38:200.
    PMID: 33995806 DOI: 10.11604/pamj.2021.38.200.19978
    Introduction: endometrial carcinoma (EC) is the seventh most common cancer in females in Malaysia, of which the majority is composed of lower grade type I EC. Although less prevalent, type II EC which is of higher grade has poorer outcome and prognosis. Human epidermal growth factor receptor 2 (HER2) is one of the possible prognostic molecular markers which can be a target for immunotherapy. This study aimed to assess the expression of HER2 in common type of EC in the local population and to determine its correlation with the clinicopathological features.

    Methods: a total of 53 cases of endometrioid type of EC were selected within a six-year period comprising of 22 cases of grade 1, 25 cases of grade 2 and six cases of grade 3 carcinoma. The selected whole tumour tissue sections were immune-stained with HER2 antibody. The scoring was semi-quantitatively analyzed based on 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for the scoring of HER2 in breast cancer.

    Results: all cases regardless of grades of endometrioid carcinoma showed negative expression of HER2 (score 0).

    Conclusion: there was no significant HER2 expression in endometrioid carcinoma. However, a follow-up study with a larger number of samples from different type of endometrial carcinoma is needed. Testing of several tumour tissue blocks to assess possible tumour heterogeneity, as well as correlation with HER2 gene amplification status by in-situ-hybridisation, are also recommended.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic
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