Marie C Lin

Shenzhen University, Bao'an, Guangdong, China

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Publications (78)381.95 Total impact

  • Wing-Fu Lai · Marie C Lin
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    ABSTRACT: Folic acid (FA) has high affinity to the folate receptors (FRs), which have three isoforms: FRα, FRβ and FRγ. Among them, FRα is a tumor specific receptor, as it is frequently over-expressed in diverse malignancies but not in normal tissues. In this study, we conjugating FA to a chitosan-poly(ethylenimine) copolymer (designated as "CP1.3K-FA"), and confirmed its low cytotoxicity and high transfection efficiency in cancer cells. Furthermore, the transfection efficiency of CP1.3K-FA/ plasmid polyplex was significantly higher than that of the unmodified copolymer in the presence of serum, suggesting its potential use as gene delivery vector in vivo. The luciferase activity assay indicated that the transfection efficiency of CP1.3K-FA was comparable to that of Fugene HD in B16 and U87 cells. This, together with the high safety profiles of CP1.3K-FA in biological systems, indicated that CP1.3K-FA warrants further development as a vector for gene delivery in cancer cells.
    No preview · Article · Aug 2015 · Current Gene Therapy
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    ABSTRACT: Interferon-induced transmembrane protein 1 (IFITM1) is one of the interferon-induced transmembrane protein family members. In this study, we reported that the elevated IFITM1 expression in human colorectal cancer (CRC) significantly correlated with CRC lymph node and distance metastasis as well as a more advanced clinical stage. Importantly, elevated IFITM1 expression is an independent prognostic factor for poor survival. To investigate the molecular mechanisms, we showed that over-expression of IFITM1 in CRC cells promoted, whereas knockdown of IFITM1 expression inhibited cell migration/invasion and tumorigenicity in vitro. Furthermore, we identified Caveolin-1 (CAV1) as a downstream target of IFITM1-induced cell invasion, as knockdown of CAV1 abrogated siIFITM1 mediated inhibition of cell invasion in CRC cells. In addition, in a CRC cohort of 229 patients, the expression of IFITM1 inversely correlated with the expression of CAV1. These results suggested that IFITM1 promotes the aggressiveness of CRC cells, and it is a potential prognostic marker and therapeutic target for CRC. Copyright © 2015. Published by Elsevier Ireland Ltd.
    No preview · Article · Aug 2015 · Cancer letters
  • Wing-Fu Lai · Marie C Lin
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    ABSTRACT: IntroductionCutaneous aging is a multifactorial process affecting different constituents of the skin (Reddy and Gilchrest 2011). During aging, distribution of subcutaneous fat is altered. The subcutaneous fat is significantly lost from the dorsum of the hand, face and shin, but accumulates in the waist or thigh (Kligman et al.1985; Farage et al.2007). In the epidermis, signs of aging include lowering of the levels of collagen IV and collagen VII at the basement membrane, flattening of the rete ridge, thinning of the epidermis, and lowering of the levels of ceramides, free fatty acids, squalene and epidermal cholesterol (El-Domyati et al.2002; Hayashi et al.2003; Sandby-Moller et al.2003; Neerken et al.2004; Fore 2006). In the dermis, aging leads to fragmentation of elastin, an increase in collagen degradation, and a decrease in production of dermal collagen, proteoglycans and glycosaminoglycans (Giacomoni et al.2000; El-Domyati et al.2002; Carrino et al.2003; Fore 2006; Varani et al. ...
    No preview · Article · Jun 2015 · Journal of Biosciences
  • Wing-Fu Lai · Marie C Lin

    No preview · Article · Jun 2015 · Journal of Biosciences
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    Wing-Fu Lai · Marie C. Lin
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    ABSTRACT: Combined chemo-gene therapy is one of the treatment modalities that have attracted extensive research interests; however, there is little information regarding the influence of drug application on gene transfer. This study bridges this gap by examining how chemotherapeutic drugs (teniposide, cis-diamminedichloroplatinum(II) and temozolomide) interfere with polyplex formation and transfection of chitosan-graft-poly(ethylenimine). Our results indicate that the degree of drug interference varies with the mechanism of drug action, with the transgene expression being severely suppressed when the plasmid is co-delivered with cis-diamminedichloroplatinum(II) or teniposide but not temozolomide. In addition, the interference with transfection by drugs varies with different gene/drug co-formulations. This is the first study to evidence that, though combined chemo-gene therapy has therapeutic potential, some chemotherapeutic drugs may reduce the treatment efficiency of gene therapy.
    Preview · Article · May 2015 · PLoS ONE
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    ABSTRACT: SNPs in human AFP promoter are associated with serum AFP levels in hepatocellular carcinoma (HCC), suggesting that AFP promoter variants may generate better transcriptional activities while retaining high specificity to AFP-producing cells. We sequenced human AFP promoters, cloned 15 different genotype promoters and tested their reporter activities in AFP-producing and non-producing cells. Among various AFP variant fragments tested, EA4D exhibited the highest reporter activity and thus was selected for the further study. EA4D was fused with tBid and coupled with nano-particle vector (H1) to form pGL3-EA4D-tBid/H1. pGL3-EA4D-tBid/H1 could express a high level of tBid while retain the specificity to AFP-producing cells. In a HCC tumor model, application of pGL3-EA4D-tBid/H1 significantly inhibited the growth of AFP-producing-implanted tumors with minimal side-effects, but had no effect on non-AFP-producing tumors. Furthermore, pGL3-EA4D-tBid/H1 could significantly sensitize HCC cells to sorafenib, an approved anti-HCC agent. Collectively, pGL3-EA4D-tBid/H1, a construct with the AFP promoter EA4D and the novel H1 delivery system, can specifically target and effectively suppress the AFP-producing HCC. This new therapeutic tool shows little toxicity in vitro and in vivo and it should thus be safe for further clinical tests.
    Full-text · Article · Apr 2014 · Experimental Cell Research
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    ABSTRACT: Gliomas are the most common and aggressive primary tumors in the central nervous system. Recently, Max interactor-1 (MXI1), an antagonist of c-Myc that is involved in brain tumor progression, has been reported to be deregulated in a variety of tumors including glioma. However, the mechanism of MXI1 deregulation in gliomas remains unclear. In this study, we show that the relative expression level of MXI1 is markedly down-regulated in glioma cell lines. Using integrated bioinformatic analysis and experimental confirmation, we identified several miRNAs by screening a panel of predicted miRNAs that may regulate the MXI1 3'UTR. The strongest inhibitory miRNA, miR-155, can attenuate the activity of a luciferase reporter gene that is fused with the MXI1 3'UTR and decrease the expression levels of MXI1 mRNA and protein in U87 glioma cells. The potential role of miR-155 in promoting glioma cell proliferation by targeting MXI1 was confirmed in various glioma cell lines by rescue experiments using MTT assays, EdU incorporation assay, and cell counting experiments. In addition, we determined that the level of MXI1 mRNA was inversely correlated with the expression of miR-155 in 18 sets of glioblastoma multiforme specimens. These findings reveal for the first time that the targeting of MXI1 by miR-155 may result in a reduction in MXI1 expression and promote glioma cell proliferation; this result suggests a novel function of miR-155 in targeting MXI1 in glioma-genesis.
    Preview · Article · Dec 2013 · PLoS ONE
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    Full-text · Article · Dec 2013 · Jokull
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    ABSTRACT: MicroRNAs (miRNAs) are small, non-coding RNAs which regulate gene expression at the post-transcriptional level. Abnormal expression of miRNAs occurs frequently in human tumors. Despite the fact that reduced expression of miR-128 has been observed in glioma tissues and cells, the role of miR-128 in tumors has not been fully characterized. In the present study, cell adhesion assays indicated that overexpression of miR-128 can promote cell-cell adhesion. Target site prediction algorithms indicated that miR-128 binds the 3'-untranslated regions of erythropoietin-producing hepatocellular receptor (Eph)B1 and EphB2 mRNAs. Luciferase reporter assays confirmed that miR-128 binds and regulates EphB1 and EphB2 mRNAs. Overexpression of EphB2 reduced the ability of miR-128 to promote cell-cell adhesion. The wound-healing assay indicated that miR-128 significantly inhibited cell migration via EphB2. This study revealed the novel functions of miR-128 in cell-cell adhesion and cell migration in glioma cells through the regulation of EphB2, and identified EphB1 and EphB2 as novel miR-128 targets.
    Preview · Article · Jul 2013 · Oncology Reports
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    Full-text · Article · May 2013 · Gastroenterology

  • No preview · Article · May 2013 · Gastroenterology
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    ABSTRACT: Chemoradiotherapy (CRT) is a standard treatment for esophageal squamous cell carcinoma (ESCC) in its advanced stages. The telomerase/telomere interacting protein PinX1 contributes to telomere maintenance, tumorigenicity and influences the DNA damage agents-induced apoptotic response in telomerase-positive cancer cells. However, the clinical and biological significance of PinX1 in human ESCCs remains unclear. We examined the expression dynamics of PinX1 by immunohistochemistry in a learning cohort (n = 98) and a validation cohort (n = 59) of ESCC patients treated with definite chemoradiotherapy (CRT). A series of in vivo and in vitro assays were performed to elucidate the effect of PinX1 on ESCC cells CRT response and underlying mechanisms. Knockdown of PinX1 did not affect ESCC cells chemosensitivities to 5-fluorouracil and cisplatin, but substantially increased ESCC cells therapeutic efficacy of radiation both in vitro and in vivo. Ectopic overexpression of PinX1 dramatically enhanced ESCC cells resistance to radiotherapy. Furthermore, we demonstrated that PinX1 resistance to radiotherapy (RT) was attributed to PinX1 maintaining telomere stability, reducing ESCC cell death by RT-induced mitosis catastrophe (MC). High expression of Pinx1 correlated positively with ESCC's resistance to CRT, and was a strong and independent predictor for short disease-specific survival (DSS) of ESCC patients. Our data suggests that PinX1 could be served as a novel predictor for a CRT response to ESCC patients, and the pathway of PinX1-mediated telomere stability might represent a new target to improve the RT effect of ESCC. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    No preview · Article · Apr 2013 · The Journal of Pathology
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    ABSTRACT: The recombinant adenovirus is evolving as a promising gene delivery vector for gene therapy due to its efficiency in transducing different genes into most types of cells. However, the host-immune response elicited by primary inoculation of an adenovirus can cause rapid clearance of the vector, impairing the efficacy of the adenovirus and hence obstructing its clinical application. We have previously synthesized a biodegradable co-polymer consisting of a low molecular weight PEI (MW 600 Da), cross-linked with β-cyclodextrin, and conjugated with folic acid (PEI-CyD-FA, named H1). Here we report that coating the adenovirus vector (Adv) with H1 (H1/rAdv) could significantly improve both the efficacy and biosafety of Adv. Enhanced transfection efficiency as well as prolonged duration of gene expression were clearly demonstrated either by intratumoral or systemic injection of a single dose of H1/rAdv in immunocompetent mice. Importantly, repeated injections of H1/rAdv did not reduce the transfection efficiency in immunocompetent mice. Furthermore, H1 transformed the surface charge of the adenovirus capsomers from negative to positive in physiological solution, suggesting that H1 coated the capsid protein of the adenovirus. This could shelter the epitopes of capsid proteins of the adenovirus, resulting in a reduced host-immune response and enhanced transfection efficiency. Taken together, these findings suggest that H1/rAdv is an effective gene delivery system superior to the adenovirus alone and that it could be considered as a preferred vehicle for gene therapy.
    Full-text · Article · Mar 2013 · Current Medicinal Chemistry
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    ABSTRACT: MiR-145 is known as a tumor suppressor in numerous human cancers. However, its role in tumor angiogenesis remains poorly defined. In this study, we found that miR-145 was significantly downregulated in breast cancer tissues by using 106 cases of normal and cancer tissues as well as in breast cancer cells. MiR-145 exhibited inhibitory role in tumor angiogenesis, cell growth and invasion and tumor growth through the post-transcriptional regulation of the novel targets N-RAS and VEGF-A. In addition, we provide evidence that the expression levels of miR-145 correlate inversely with malignancy stages of breast tumors, although there is no association between miR-145 levels and hormone receptor levels in breast cancer. Taken together, these results demonstrate that miR-145 plays important inhibitory role in breast cancer malignancy by targeting N-RAS and VEGF-A, which may be potential therapeutic and diagnostic targets.
    Full-text · Article · Jun 2012 · Cell cycle (Georgetown, Tex.)
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    ABSTRACT: In this study we describe a novel polymer, mPPS-FA, synthesized as a potential gene transfer vector. To complete mPPS-FA, folic acid was conjugated to a backbone (named mPPS) consisting of a copolymer of methyl PEG-2000, PEI-600, and sebacoyl chloride. (1)H NMR, FT-IR, and UV spectroscopy were used to characterize the structure of mPPS-FA. It was revealed that mPPS-FA holds the ability to bind plasmid DNA yielding positively charged particles (polyplexes). Dynamic light scattering (DLS) and TEM techniques were used to study the size and morphology of the formed mPPS-FA/DNA nanocomplexes. The mPPS-FA/DNA nanoparticles exhibited low cytotoxicity as transfection of B16-F0, U87MG, CHO-1, and Ho-8910 cells produced >80% viability indicating low cytotoxicity of the polymer. The ability of mPPS-FA to deliver EGFP plasmid to melanoma B16-F0, U87, CHO-1, Ho-8910, and A549 cells was investigated in vitro as compared to the lipid-based transfection agent Lipofectamine2000 and Linear PEI 22 kDa (L-PEI 22 kDa). We found that mPPS-FA/DNA complexes yielded the highest GFP transfection efficiency in B16-F0, U87, CHO-1, and Ho-8910 cells, which all highly express folate receptors (FR), at an mPPS-FA/DNA ratio (w/w) of 15. Furthermore, the transfection of mPPS-FA/DNA complexes in CHO-1 cells could be competitively blocked by free folic acid molecules. In contrast, in low FR expressing A549 cells, mPPS-FA showed similar low transfection efficiency as mPPS. Taken together, mPPS-FA showed the highest efficiency in vitro and the potential to be developed as a nonviral gene carrier.
    No preview · Article · Apr 2012 · International Journal of Pharmaceutics
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    ABSTRACT: The recent outbreak of enterovirus 71 (EV71) infected millions of children and caused over 1,000 deaths. To date, neither an effective vaccine nor antiviral treatment is available for EV71 infection. Interferons (IFNs) have been successfully applied to treat patients with hepatitis B and C viral infections for decades but have failed to treat EV71 infections. Here, we provide the evidence that EV71 antagonizes type I IFN signaling by reducing the level of interferon receptor 1 (IFNAR1). We show that the host cells could sense EV71 infection and stimulate IFN-β production. However, the induction of downstream IFN-stimulated genes is inhibited by EV71. Also, only a slight interferon response and antiviral effects could be detected in cells treated with recombinant type I IFNs after EV71 infection. Further studies reveal that EV71 blocks the IFN-mediated phosphorylation of STAT1, STAT2, Jak1, and Tyk2 by reducing IFNAR1. Finally, we identified the 2A protease encoded by EV71 as an antagonist of IFNs and show that the protease activity is required for reducing IFNAR1 levels. Taken together, our study for the first time uncovers a mechanism used by EV71 to antagonize type I IFN signaling and provides new targets for future antiviral strategies.
    Full-text · Article · Jan 2012 · Journal of Virology
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    ABSTRACT: miR-124 is a brain-enriched microRNA that plays a crucial role in neural development and has been shown to be down-regulated in glioma and medulloblastoma, suggesting its possible involvement in brain tumor progression. Here, we show that miR-124 is down-regulated in a panel of different grades of glioma tissues and in all of the human glioma cell lines we examined. By integrated bioinformatics analysis and experimental confirmation, we identified SNAI2, which is often up-regulated in glioma, as a direct functional target of miR-124. Because SNAI2 has been shown to regulate stem cell functions, we examined the roles of miR-124 and SNAI2 in glioma cell stem-like traits. The results showed that overexpression of miR-124 and knockdown of SNAI2 reduced neurosphere formation, CD133(+) cell subpopulation, and stem cell marker (BMI1, Nanog, and Nestin) expression, and these effects could be rescued by re-expression of SNAI2. Furthermore, enhanced miR-124 expression significantly inhibited glioma cell invasion in vitro. Finally, stable overexpression of miR-124 and knockdown of SNAI2 inhibited the tumorigenicity and invasion of glioma cells in vivo. These findings reveal, for the first time, that the tumor suppressor activity of miR-124 could be partly due to its inhibitory effects on glioma stem-like traits and invasiveness through SNAI2.
    Preview · Article · Jan 2012 · Journal of Biological Chemistry
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    ABSTRACT: miR-124 is a brain-enriched miRNA that plays crucial role in neural development and has been shown to be downregulated in glioma and medulloblastoma, suggesting its possible involvement in brain tumor progression. Here we show that miR-124 is down-regulated in a panel of different grades of glioma tissues and all of the human glioma cell lines we examined. By integrated bioinformatics analysis and experimental confirmation, we identified SNAI2, which is often upregulated in glioma, as a direct functional target of miR-124. Since SNAI2 has been shown to regulate stem cell functions, we examined the roles of miR-124 and SNAI2 in glioma stem-like cell traits. The results showed that overexpression of miR-124 and knockdown of SNAI2 reduced neurosphere formation, CD133+ cell subpopulation and stem cell markers (BMI1, Nanog and Nestin) expressions, and these effects could be rescued by re-expression of SNAI2. Furthermore, enhanced miR-124 expression significantly inhibited glioma cell invasion in vitro. Finally, stable overexpression of miR-124 and knockdown of SNAI2 inhibited the tumorigenicity and invasion of glioma cells in vivo. These findings reveal for the first time the tumor suppressor activity of miR-124 could be partly due to its inhibitory effects on glioma stem-like traits and invasiveness through SNAI2.
    No preview · Article · Jan 2012 · Journal of Biological Chemistry
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is a highly malignant cancer with local invasion and early distant metastasis. NPC is highly prevalent in the Southern China and South-eastern Asia. The genetic susceptibility, endemic environment factors, and Epstein-Barr virus (EBV) infection are believed to be the major etiologic factors of NPC. Once metastasis occurs, the prognosis is very poor. It is urgently needed to develop biomarkers for early clinical diagnosis/prognosis, and novel effective therapies for nasopharyngeal carcinoma. In this paper, we systematically reviewed the current progress of miRNA studies in NPC. It has been shown that both host encoded miRNAs and EBV encoded miRNAs play key roles in almost all the steps of epithelia cell carcinogenesis, including epithelial-mesenchymal to stem-like transition, cell growth, migration, invasion, and tumorigenesis. More importantly, some miRNAs could be secreted out and play a role in the microenvironments. The level of sera miRNAs is correlated with the copy numbers of host miRNAs in tumor biopsies. Promising results of gene therapy have been also achieved by lentiviral delivered miRNAs. Taken together, cell free miRNAs would be potential biomarkers of early clinical diagnosis/prognosis; while some miRNAs could be further developed into therapeutic agents in the future.
    No preview · Article · Sep 2011 · Biochimica et Biophysica Acta
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    ABSTRACT: The authors have previously isolated a putative oncogene, eukaryotic initiation factor 5A2 (EIF5A2) from 3q26. In this study, EIF5A2 was characterised for its role in colorectal carcinoma (CRC) aggressiveness and underlying molecular mechanisms. The expression dynamics of EIF5A2 were examined by immunohistochemistry in a cohort of carcinomatous and non-neoplastic colorectal tissues and cells. A series of in-vivo and in-vitro assays was performed to elucidate the function of EIF5A2 in CRC and its underlying mechanisms. The overexpression of EIF5A2 was examined by immunohistochemistry in 102/229 (44.5%) CRC patients, and it was significantly correlated with tumour metastasis and determined to be an independent predictor of shortened survival (p<0.05). Ectopic overexpression of EIF5A2 in CRC cells enhanced cell motility and invasion in vitro and tumour metastasis in vivo, and induced epithelial-mesenchymal transition (EMT). The depletion of EIF5A2 expression prevented CRC cell invasiveness and inhibited EMT. Importantly, the metastasis-associated protein 1 (MTA1) gene was identified as a potential downstream target of EIF5A2 in CRC cells, and knockdown of MTA1 eliminated the augmentation of carcinoma cell migration, invasion and EMT by ectopic EIF5A2. The overexpression of EIF5A2 in CRC cells substantially enhanced the enrichment of c-myc on the promoter of MTA1, and MTA1 upregulation by EIF5A2 was partly dependent on c-myc. The data suggest that EIF5A2 plays an important oncogenic role in CRC aggressiveness by the upregulation of MTA1 to induce EMT, and EIF5A2 could be employed as a novel prognostic marker and/or effective therapeutic target for CRC.
    No preview · Article · Aug 2011 · Gut

Publication Stats

2k Citations
381.95 Total Impact Points

Institutions

  • 2015
    • Shenzhen University
      Bao'an, Guangdong, China
  • 2010-2014
    • The Chinese University of Hong Kong
      • • Department of Surgery
      • • State Key Laboratory of Oncology in South China
      • • Department of Chemistry
      Hong Kong, Hong Kong
  • 2011-2013
    • Third Military Medical University
      • Institute of Pathology and Southwest Cancer Center
      Ch’ung-ch’ing-shih, Chongqing Shi, China
    • Sun Yat-Sen University Cancer Center
      • Department of Radiation Oncology
      Shengcheng, Guangdong, China
  • 2007-2012
    • East China Normal University
      Shanghai, Shanghai Shi, China
  • 2002-2010
    • The University of Hong Kong
      • Department of Chemistry
      Hong Kong, Hong Kong
    • Fuerkang Beijing Institute of Biotechnology
      Peping, Beijing, China
  • 2008
    • Hefei University of Technology
      Luchow, Anhui Sheng, China
  • 2006
    • Nanfang Hospital
      Shengcheng, Guangdong, China