MicroRNA-214 Regulates the Acquired Resistance to Gefitinib via the PTEN/AKT Pathway in EGFR-mutant Cell Lines

Wang, Yong-Sheng,Wang, Yin-Hua,Xia, Hong-Ping,Zhou, Song-Wen,Schmid-Bindert, Gerald,Zhou, Cai-Cun Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.1

Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.

Oral administration of Schisandra chinensis extract suppresses Dnmt1 expression in Kunming mice ovaries

Wen-yong Li,Feng-Rui Wu,Deng-kun Li,Mi-mi Su,Yong Liu,Biao Ding,Rong Wang 한국유전학회 2016 Genes & Genomics Vol.38 No.12

The plant Schisandra chinensis contains a phytoestrogens, a type of naturally occurring estrogens which have multiple functions in a number of biological processes. To investigate the correlation between phytoestrogens and epigenetic modification, especially the effect of phytoestrogens on DNA methylation, sexually healthy female mice were used as an animal model in the present study. Briefly, the total RNA and protein were isolated from the ovary of mice after 7-day oral administration of Schisandra chinensis extract (SCE), while distilled water was given to the animals in the control group. Real-time PCR, Western blotting, and enzyme activity assays were performed to examine the effect of the extract of S. chinensis on Dnmt1 transcription and activity. A promoter assay was further conducted in MCF cells (ER positive) to explore also the influence of SCE on Dnmt1 transcriptional activity. The results revealed that the mRNA and protein expression levels of mouse Dnmt1 were both significantly downregulated in the treated group. The transcription of Dnmt1 was suppressed by SCE and in the E2-added group also. Meanwhile the numbers of oocytes at different stages were increased in the treated group when compared by histological analyses with those in the control group. Taken together, the results indicated that, similarly to the action of estrogen, phytoestrogens affected Dnmt1 transcription in mammals, regulating the related gene expression and cell differentiation. The findings of our examination provided also basic data and understanding for the correlation between phytoestrogens and epigenetic modification.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells

Xiong, Wei,Jiang, Yong-Xin,Ai, Yi-Qin,Liu, Shan,Wu, Xing-Rao,Cui, Jian-Guo,Qin, Ji-Yong,Liu, Yan,Xia, Yao-Xiong,Ju, Yun-He,He, Wen-Jie,Wang, Yong,Li, Yun-Fen,Hou, Yu,Wang, Li,Li, Wen-Hui Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

MLH1 Polymorphisms and Cancer risk: a Meta-analysis Based on 33 Case-control Studies

Xu, Jia-Li,Yin, Zhi-Qiang,Huang, Ming-De,Wang, Xie-Feng,Gao, Wen,Liu, Ling-Xiang,Wang, Rong-Sheng,Huang, Pu-Wen,Yin, Yong-Mei,Liu, Ping,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations. Methods: Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations. Results: Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model. Conclusions: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.

Syntheses, Structure, and Properties of Four Metal-Organic Polymers Based on Rigid Multiple Carboxylate Ligands and N-Donor Ligands

Yong Zhou,Wen-Hao Zhao,Jin Wang,Jin-Rui Wei,Xian-Hong Yin,Xiang-Bo Wei,Cui-Wu Lin 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.11

Four metal-organic coordination polymers, {[Cd2(BIBP)2(H2DTDA)2]n  · 2(H2O)} (1), [Zn (BIBP) (H2TDA)2] n (2), [Cd2(BIBP)(H2TDA)2] n (3), and [Ni2(BIBP)2(H2DTDA)2(μ-O)] n , (4) [where BIBP = 4,4′-bis(1-imidazoly)biphenyl, H2TDA = [1,1′:4′1″-terphen-yl]-3,3″-dicarboxylic acid, and H2DTDA = 2′,5′-dimethyl-[1,1′:4′,1″-terphenyl]-3,3″-dicarboxylic acid] were hydrothermally synthesized and characterized by elemental analyses, IR, TG, luminescence, and single crystal X-ray diffraction. X-Ray diffraction analysis reveals that the four complexes exhibit new frameworks due to diverse coordination conformations. The different coordination modes of the ligands BIBP and two aromatic carboxylate acids play important roles in the construction of the final structure for the complexes. X-ray structure analysis reveals that 1, 2, and 4 are 3D coordination polymers, while complex 3 is a 2D network polymer.

Endothelial Aquaporin-1 (AQP1) Expression Is Regulated by Transcription Factor Mef2c

Yong Jiang,He Liu,Wen-jing Liu,Hai-bin Tong,Chang-jun Chen,Fu-gui Lin,Yan-hang Zhuo,Xiao-zhen Qian,Zeng-bin Wang,Yu Wang,Peng Zhang,Hong-liang Jia 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.4

Aquaporin 1 (AQP1) is expressed in most microvascula-ture endothelial cells and forms water channels that play major roles in a variety of physiologic processes. This study aimed to delineate the transcriptional regulation of AQP1 by Mef2c in endothelial cells. Mef2c cooperated with Sp1 to activate human AQP1 transcription by binding to its proximal promoter in human umbilical cord vein endothelial cells (HUVEC). Over-expression of Mef2c, Sp1, or Mef2c/Sp1 increased HUVEC migration and tube-forming ability, which can be abolished AQP1 knockdown. These data indicate that AQP1 is a direct target of Mef2c in regulating angiogenesis and vasculogenesis of endothelial cells.

Development of a Love Wave Based Device for Sensing Icing Process with Fast Response

Wen Wang,Yining Yin,Yana Jia,Mengwei Liu,Yong Liang,Yufeng Zhang,Minghui Lu 대한전기학회 2020 Journal of Electrical Engineering & Technology Vol.15 No.3

This work addresses the theoretical and experimental investigations of a Love wave based device employing waveguide structure of SiO2/36° YX-LiTaO3 for sensing icing process. The mass loading efect induced by the icing process modulates the acoustic wave propagation, and corresponding changes in device frequency can be collected to evaluate the icing process. The waveguide structure confnes the acoustic wave energy into SiO2 thin-flm, which contributes well to the improvement of the mass loading sensitivity. The corresponding sensing mechanism was analyzed by solving the acoustic propagation equations in layered structure. The sensing device patterned by delay-line on 36° YX-LiTaO3 substrate with SiO2 guiding layer was photolithographically developed as the sensor element, and characterized by using the high-low temperature chamber. The icing process was simulated by dropping appropriate water on top of the device surface. Very clear and fast frequency response was observed from the proposed sensing device in the icing process, and also, the infuence of SiO2 guiding layer thickness on sensor response was also investigated.

Synthesis and DNA-binding Properties of Trehalose-tethered Monomeric and Dimeric Berberines

Wang, Yong-Min,Zhou, Chun-Qiong,Chen, Jin-Xiang,Chen, Wen-Hua Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.3

Trehalose-tethered monomeric and dimeric berberines were synthesized in 50% and 30% from the reaction of berberrubine with 6-tosyl-${\alpha}$,${\alpha}^{\prime}$-trehalose and 6,6'-ditosyl-${\alpha}$,${\alpha}^{\prime}$-trehalose, respectively, and fully characterized by MS (HR and ESI) and NMR ($^1H$, $^{13}C$, COSY and HSQC). Spectrophotometric and spectrofluorimetric titrations indicated that compared with berberine, trehalose-tethered monomeric berberine had comparable DNA-binding affinity toward calf-thymus DNA, whereas trehalose-spaced dimeric berberine exhibited higher DNA-binding affinity. The potential application of these conjugates is also briefly discussed.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Yong-Ping Chen,Feng-Bin Lu,Da-Zhi Chen,Lu Chen,En-De Hu,Jin-Lu Wu,Hui Li,Yue-Wen Gong,Zhuo Lin,Xiao-Dong Wang,Ji Li,Xiao-Ya Jin,Lan-Man Xu 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Construction and Expression of an Eukaryotic Expression Vector Containing the IER3 Gene

Wang, Zhen,Yu, Hong-Sheng,Yao, Ru-Yong,Qiu, Wen-Sheng,Yue, Lu,Sui, Ai-Hua,Liu, Xiang-Ping,Liu, Shi-Hai Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: More and more research indicate that the immediately early response gene 3 (IER3) is involved inmany biological provesses, such as apoptosis and immunoreaction, as well as viral infection, tumorigenesis and tumour progression. Methods: Here we describe the construction of an eukaryotic expression vector containing IER3 gene and its expression in A549 cells as assessed through fluorescence microscopyand Western-blotting. Results: Fluorescence detection displayed that GFP in cytoplasm was high during 48 and 72 hours post-transfection. In addition, Western blotting showed significant increase in IER3 gene expression in the transfected cells compared with controls. Conclusion: The recombinate plasmid expression vector was constructed successfully, which may provide a basis for further exploration of function of IER3 in lung cancer.