Publications by authors named "Sen Lian"

53 Publications

Natural Phytochemicals in Bladder Cancer Prevention and Therapy.

Front Oncol 2021 30;11:652033. Epub 2021 Apr 30.

Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, South Korea.

Phytochemicals are natural small-molecule compounds derived from plants that have attracted attention for their anticancer activities. Some phytochemicals have been developed as first-line anticancer drugs, such as paclitaxel and vincristine. In addition, several phytochemicals show good tumor suppression functions in various cancer types. Bladder cancer is a malignant tumor of the urinary system. To date, few specific phytochemicals have been used for bladder cancer therapy, although many have been studied in bladder cancer cells and mouse models. Therefore, it is important to collate and summarize the available information on the role of phytochemicals in the prevention and treatment of bladder cancer. In this review, we summarize the effects of several phytochemicals including flavonoids, steroids, nitrogen compounds, and aromatic substances with anticancer properties and classify the mechanism of action of phytochemicals in bladder cancer. This review will contribute to facilitating the development of new anticancer drugs and strategies for the treatment of bladder cancer using phytochemicals.
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http://dx.doi.org/10.3389/fonc.2021.652033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120318PMC
April 2021

Nanomedicine-based cancer immunotherapy: recent trends and future perspectives.

Cancer Gene Ther 2021 Sep 8;28(9):911-923. Epub 2021 Feb 8.

Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab Emirates.

The combination of cancer immunotherapy with efficient functionalized nanosystems has emerged as a beneficial treatment strategy and its use has increased rapidly. The roles of stimuli-responsive nanosystems and nanomedicine-based cancer immunotherapy, a subsidiary discipline in the field of immunology, are pivotal. The present era is witnessing rapid advancements in the use of nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. The development of cancer nanomedicine has posthaste ratified the outcomes of immunotherapy to the subsequent stage in the current era of medical research. This review focuses on key findings with respect to the effectiveness of nanomedicine-based cancer immunotherapies and their applications, which include i) immune checkpoint inhibitors and nanomedicine, ii) CRISPR-Cas nanoparticles (NPs) in cancer immunotherapy, iii) combination cancer immunotherapy with core-shell nanoparticles, iv) biomimetic NPs for cancer immunotherapy, and v) CAR-T cells and cancer nanoimmunotherapy. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.
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http://dx.doi.org/10.1038/s41417-021-00299-4DOI Listing
September 2021

Butylated Hydroxytoluene Induced Resistance Against in Apple Fruit.

Front Microbiol 2020 14;11:599062. Epub 2021 Jan 14.

Key Laboratory of Integrated Crop Pest Management of Shandong Province, College of Plant Health and Medicine, Qingdao Agricultural University, Qingdao, China.

Apple ring rot caused by is an important disease in China, which leads to serious economic losses during storage. Plant activators are compounds that induce resistance against pathogen infection and are considered as a promising alternative strategy to traditional chemical treatment. In the present study, butylated hydroxytoluene (BHT), a potential plant activator, was evaluated for its induced resistance against in postharvest apple fruits. The physiological and molecular mechanisms involved in induced resistance were also explored. The results showed that BHT treatment could trigger strong resistance in apple fruits against , and the optimum concentration was 200 μmol L by immersion of fruits. BHT treatment significantly increased the activities of four defensive enzymes and alleviated lipid peroxidation by increasing antioxidant enzyme activities. In addition, salicylic acid (SA) content was enhanced by BHT treatment as well as the expression of three SA biosynthesis-related genes (, , and ) and two defense genes ( and ). Our results suggest that BHT-conferred resistance against might be mainly through increasing the activities of defense-related enzymes and activating SA signaling pathway, which may provide an alternative strategy to control apple ring rot in postharvest fruits.
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http://dx.doi.org/10.3389/fmicb.2020.599062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840594PMC
January 2021

Progression of symptoms caused by Botryosphaeria dothidea on apple branches.

Phytopathology 2021 Jan 24. Epub 2021 Jan 24.

Qingdao Agricultural University, 98431, College of Plant Health and Medicine, Qingdao, Shandong, China;

Until recently, the causal agent of Botryosphaeria canker was assumed to differ from that causing ring rot on fruit and warts on branches on apple trees in China and East Asia. However, recent research documented that Botryosphaeria dothidea caused both disease symptoms on apple. Inoculations with strains isolated from cankers and warts on branches were conducted to investigate symptom progression caused by B. dothidea and conditions inducing the two symptom types. The results confirmed that both cankers and warts are caused by B. dothidea. Warts are the results of hyperplasia and suberization of bark tissues induced by fungal infection, whereas cankers result from the rapid growth of hyphae from inside warts, lenticels or wounds. Resistance to B. dothidea exists in living apple branches. When a living branch is infected via lenticels, the pathogen induces proliferation and suberization of cortical cells that restricts the growth and expansion of the hyphae, leading to wart symptom. However, under certain stress conditions such as drought, the hyphae inside host tissues expand rapidly and kill cortical cells, leading to canker development. Host resistance may recover during active growth periods, which suppresses or even stops rapid expansion of the hyphae, leading to the intermediate symptom of canker warts. Abiotic factors, such as drought or high temperature in early spring, can result in rapid extension of colonized hyphae in branches and conversion of warts to cankers. Preventing this transition can be an important measure in managing Botryosphaeria canker on apple.
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http://dx.doi.org/10.1094/PHYTO-12-20-0551-RDOI Listing
January 2021

Suppression of Urokinase-Type Plasminogen Activator Receptor by Docosahexaenoic Acid Mediated by Heme Oxygenase-1 in 12--Tetradecanoylphorbol-13-Acetate-Induced Human Endothelial Cells.

Front Pharmacol 2020 26;11:577302. Epub 2020 Nov 26.

Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Korea.

Urokinase-type plasminogen activator receptor (uPAR) plays a crucial role in inflammation and tumor metastasis. Docosahexaenoic acid (DHA), a representative omega-3 polyunsaturated fatty acid, has been shown to exhibit anti-inflammatory and anti-tumor properties. However, the mechanism by which DHA negatively regulates uPAR expression is not yet understood. The aim of this study was to investigate the effect of DHA on 12--tetradecanoylphorbol-13-acetate (TPA)-induced uPAR expression and potential role of heme oxygenase-1 (HO-1) in DHA-induced inhibition of uPAR in human endothelial ECV304 cells. Results showed that TPA induced uPAR expression in a time dependent manner, while DHA inhibited uPAR expression in a concentration-dependent manner. Moreover, treatment with DHA induced HO-1 expression in a time- and concentration-dependent manner. In addition, DHA-induced inhibition of uPAR expression and cell invasion in TPA-stimulated cells was reversed by si-HO-1 RNA. Induction of HO-1 by ferric protoporphyrin IX (FePP) inhibited TPA-induced uPAR expression, and this effect was abolished by treatment with the HO-1 inhibitor tin protoporphyrin IX (SnPP). Additionally, carbon monoxide, an HO-1 product, attenuated TPA-induced uPAR expression and cell invasion. Collectively, these data suggest a novel role of DHA-induced HO-1 in reducing uPAR expression and cell invasion in human endothelial ECV304 cells.
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http://dx.doi.org/10.3389/fphar.2020.577302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768974PMC
November 2020

Biocontrol efficiency of Meyerozyma guilliermondii Y-1 against apple postharvest decay caused by Botryosphaeria dothidea and the possible mechanisms of action.

Int J Food Microbiol 2021 Jan 6;338:108957. Epub 2020 Nov 6.

College of Plant Health and Medicine, Key Laboratory of Integrated Crop Pest Management of Shandong Province, Shandong Province Key Laboratory of Applied Mycology, Qingdao Agricultural University, Qingdao, Shandong 266109, China. Electronic address:

Apple ring rot, caused by Botryosphaeria dothidea, is one of the important diseases in China. This pathogen infects branches and fruit and also results in fruit decay during storage. Biocontrol agents have been proposed to reduce apple decays during storage and are considered as a promising alternative strategy to traditional chemical treatment. In this study, Meyerozyma guilliermondii Y-1, isolated from healthy grape fruit, was firstly evaluated for its biocontrol efficiency against B. dothidea in postharvest apple fruit, and the possible mechanisms were investigated. The results revealed that M. guilliermondii Y-1 treatment effectively reduced apple ring rot caused by B. dothidea in vivo. The disease incidence and lesion diameter were reduced by 32.22% and 57.51% compared with those of control fruit. Furthermore, the use of filtrate and autoclaved culture of M. guilliermondii Y-1 also showed a certain degree of control efficiency against fruit ring rot. M. guilliermondii Y-1 significantly inhibited the mycelial growth and spore generation of B. dothidea in vitro and exhibited an obvious ability to colonize in apple fruit wounds and surface at 25 °C or 4 °C. In addition, M. guilliermondii Y-1 treatment significantly enhanced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), phenylalanine ammonialyase (PAL), and polyphenoloxidase (PPO), promoted the total phenolics content, and alleviated lipid peroxidation in apple fruit. As expected, we found that the expression of four pathogenesis-related proteins genes (MdPR1, MdPR5, MdGLU, and MdCHI) was remarkably increased by M. guilliermondii Y-1 treatment. Our data together suggest that M. guilliermondii Y-1 is a potential biocontrol agent against B. dothidea postharvest infection in apple fruit, partially through inhibiting mycelial growth and spore germination of B. dothidea, competing for space and nutrient with pathogen, and inducing resistance in apple fruit by stimulating a series of defense responses.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2020.108957DOI Listing
January 2021

Effect of Rainfall and Temperature on Perithecium Production of on Cankered Apple Branches.

Phytopathology 2021 Jul 28:PHYTO07200262R. Epub 2021 Jul 28.

College of Plant Health and Medicine, Qingdao Agricultural University; Key Lab of Integrated Crop Pests Management of Shandong Province, Qingdao, Shandong 266109, P.R. China.

is a fungal pathogen causing canker, dieback, and fruit rot of apple trees worldwide. Ascospores are an important source of inoculum of Botryosphaeria canker in China. Experiments were conducted under both controlled and natural conditions to study perithecium formation in relation to environmental conditions. Perithecia of were detected on cankered lesions throughout the apple growing season except in July and in some years including August under natural conditions. On newly formed canker lesions, the first perithecium was detected as early as August, about 1 week after rainfall. Perithecia matured successively, lasting from early August to June of the next year, with a peak in late September or early October. Temperature and rainfall are two key environmental factors affecting perithecium formation. Under controlled conditions, perithecia were produced only on cankered shoots incubated at test temperatures of 20 and 25°C and wetted by >3 days of simulated rainfall per week. The number of perithecia produced on canker lesions increased with the increase in rainfall duration. Perithecia were formed on canker shoots exposed to rainfall only in June, July, and August but not in September. Rainfall of >3 days per week can be used to predict the initial formation of perithecia in the main apple production areas in China to assist disease management.
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http://dx.doi.org/10.1094/PHYTO-07-20-0262-RDOI Listing
July 2021

Effects of Temperature and Moisture on Conidia Germination, Infection, and Acervulus Formation of the Apple Marssonina Leaf Blotch Pathogen () in China.

Plant Dis 2021 Apr 23;105(4):1057-1064. Epub 2021 Feb 23.

College of Plant Health and Medicine, Qingdao Agricultural University, and Key Laboratory of Integrated Crop Pests Management of Shandong Province, Qingdao, Shandong 266109, People's Republic of China.

Apple Marssonina leaf blotch (AMLB; ) is a severe disease of apple that mainly causes premature leaf defoliation in many apple growing areas worldwide. AMLB epidemic development is closely related to temperature and rainfall. In this study, the effects of temperature and moisture on conidium germination, infection on leaves, and acervulus production were investigated under controlled environments. The temperature required for conidium germination and infection ranged from 5 to 30°C, with the optimum at approximately 23°C. The temperature required for acervulus formation was slightly higher, with the optimum at 24.6°C. Wetness was needed in order for conidia to germinate and infect; only a few conidia germinated at 100% RH. However, lesions can produce acervuli in dry conditions. The minimum duration of leaf wetness required for conidia to complete the entire infection process was 14, 8, 4, and 6 h at 10, 15, 20, and 25°C, respectively. A model describing the effect of temperature and leaf wetness duration was built. The model estimated that the optimum temperature for conidial infection was 22.6°C and the minimum wetness duration required was 4.8 h. This model can be used to forecast conidial infection to assist in disease management in commercial apple production.
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http://dx.doi.org/10.1094/PDIS-06-20-1180-REDOI Listing
April 2021

Identification of viruses infecting six plum cultivars in Korea by RNA-sequencing.

PeerJ 2020 29;8:e9588. Epub 2020 Jul 29.

Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.

Background: Plums are a kind of stone fruit, a category that includes peaches, cherries, apricots, and almonds. In Korea, Japanese plum trees are usually cultivated as they best suit the climate. To date, there have been few studies in Korea on viruses infecting plum trees compared to those infecting peach trees.

Methods: To identify viruses and viroids infecting plum trees, we collected leaf samples from six different plum cultivars and subjected them to RNA-sequencing (RNA-seq). Six different plum transcriptomes were de novo assembled using the Trinity assembler followed by BLAST searching against a viral reference database.

Results: We identified hop stunt viroid (HSVd) and six viruses, including apple chlorotic leaf spot virus (ACLSV), little cherry virus-1 (LChV-1), peach virus D (PeVD), peach leaf pitting-associated virus (PLPaV), plum bark necrosis stem pitting-associated virus (PBNSPaV), and prunus necrotic ringspot virus (PNRSV), from six plum cultivars by RNA-seq. RT-PCR confirmed the infection of HSVd and three viruses-ACLSV, PBNSPaV, and PNRSV-in plum trees. However, RT-PCR demonstrated that plum trees in this study were not infected by LChV-1, PeVD, or PLPaV. It is likely that the three viruses LChV-1, PeVD, and PLPaV as identified by RNA-seq were contaminants from other peach libraries caused by index misassignment, which suggests that careful confirmation by other methods should be carried out in next-generation sequencing (NGS)-based virus identification. Taken together, we identified a viroid and three viruses infecting plum trees in Korea.
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http://dx.doi.org/10.7717/peerj.9588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395596PMC
July 2020

Rapid Development of Targeting circRNAs in Cardiovascular Diseases.

Mol Ther Nucleic Acids 2020 Sep 27;21:568-576. Epub 2020 Jun 27.

Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada. Electronic address:

Circular RNAs (circRNAs) are circularized, single-stranded RNAs that are covalently linked. With their abundance in tissues and developmental stage-specific expression, circRNAs participate in a variety of physiological and pathological processes. In this review, we discuss the development of circRNAs used as biomarkers and therapeutic targets for cardiovascular diseases (CVDs), focusing on recent discoveries and applications of exosomal circRNAs that highlight opportunities and challenges. Some studies have identified a spectrum of circRNAs that are differentially expressed in CVDs, while other studies further manipulated specific circRNA expression and showed an ameliorated pathogenic state such as ischemic injury, hypertrophy, and cardiac fibrosis. Studies and applications of circRNAs are being rapidly developed. We expect to see clinical use of circRNAs as biomarkers and targets for disease treatment in the near future.
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http://dx.doi.org/10.1016/j.omtn.2020.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390851PMC
September 2020

Lysophosphatidic Acid Upregulates Recepteur D'origine Nantais Expression and Cell Invasion via Egr-1, AP-1, and NF-κB Signaling in Bladder Carcinoma Cells.

Int J Mol Sci 2020 Jan 1;21(1). Epub 2020 Jan 1.

Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Korea.

Muscle invasive bladder carcinoma is a highly malignant cancer with a high mortality rate, due to its tendency to metastasize. The tyrosine kinase recepteur d'origine nantais (RON) promotes bladder carcinoma metastasis. Lysophosphatidic acid (LPA) is a phospholipid derivative, which acts as a signaling molecule to activate three high affinity G-protein coupled receptors, LPA1, LPA2, and LPA3. This in turn leads to cell proliferation and contributes to oncogenesis. However, little is known about the effects of LPA on invasive bladder cancer (IBC). In this study, we discovered that LPA upregulated RON expression, which in turn promoted cell invasion in bladder cancer T24 cells. As expected, we found that the LPA receptor was essential for the LPA induced increase in RON expression. More interestingly, we discovered that LPA induced RON expression via the MAPK (ERK1/2, JNK1/2), Egr-1, AP-1, and NF-κB signaling axes. These results provide experimental evidence and novel insights regarding bladder malignancy metastasis, which could be helpful for developing new therapeutic strategies for IBC treatment.
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http://dx.doi.org/10.3390/ijms21010304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981588PMC
January 2020

Sulforaphane Inhibits Nonmuscle Invasive Bladder Cancer Cells Proliferation through Suppression of HIF-1α-Mediated Glycolysis in Hypoxia.

J Agric Food Chem 2019 Jul 9;67(28):7844-7854. Epub 2019 Jul 9.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences , Southern Medical University , Guangzhou Guangdong , 510515 , China.

Bladder cancer is the fourth common cancer among men and more than 70% of the bladder cancer is nonmuscle invasive bladder cancer (NMIBC). Because of its high recurrence rate, NMIBC brings to patients physical agony and high therapy costs to the patients' family and society. It is imperative to seek a natural compound to inhibit bladder cancer cell growth and prevent bladder cancer recurrence. Cell proliferation is one of the main features of solid tumor development, and the rapid tumor cell growth usually leads to hypoxia due to the low oxygen environment. In this study we found that sulforaphane, a natural chemical which was abundant in cruciferous vegetables, could suppress bladder cancer cells proliferation in hypoxia significantly stronger than in normoxia ( < 0.05): 20 μM sulforaphane inhibited bladder cancer cell proliferation by 26.1 ± 4.1% in normoxia, while it inhibited cell proliferation by 39.7 ± 5.2% in hypoxia in RT112 cells. Consistently, sulforaphane inhibited cell proliferation by 29.7 ± 4.6% in normoxia, while it inhibited cell proliferation by 48.3 ± 5.2% in hypoxia in RT4 cells. Moreover, we revealed that sulforaphane decreased glycolytic metabolism in a hypoxia microenvironment by downregulating hypoxia-induced HIF-1α and blocking HIF-1α trans-localization to the nucleus in NMIBC cell lines. This study discovered a food sourced compound inhibiting bladder cancer cells proliferation and provided experimental evidence for developing a new bladder cancer preventive and therapeutic strategy.
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http://dx.doi.org/10.1021/acs.jafc.9b03027DOI Listing
July 2019

Metformin inhibits lithocholic acid-induced interleukin 8 upregulation in colorectal cancer cells by suppressing ROS production and NF-kB activity.

Sci Rep 2019 02 14;9(1):2003. Epub 2019 Feb 14.

Department of Biochemistry, Chonnam National University Medical School, Seoyang Ro 264, Hwasun, Jeonnam, 58138, Korea.

Metformin, an inexpensive, well-tolerated oral agent that is a commonly used first-line treatment for type 2 diabetes, has become the focus of intense research as a potential anticancer agent. In this study, we describe the inhibitory effect of metformin in interleukin 8 (IL-8) upregulation by lithocholic acid (LCA) in HCT116 colorectal cancer (CRC) cells. Pharmacological inhibition studies indicated that reactive oxygen species (ROS) were involved in LCA-induced IL-8 upregulation through activation of the transcription factor NF-κB. Metformin was demonstrated to block LCA-stimulated ROS production, in turn suppressing NF-κB signaling that was critical for IL-8 upregulation. An NADPH oxidase assay proved that the inhibitory effect of metformin on ROS production was derived from its strong suppression of NADPH oxidase, a key producer of ROS in cells. Compared with conditioned media (CM) derived from HCT116 cells treated with LCA, CM derived from HCT116 cells pretreated with metformin and then treated with LCA lost all stimulatory effect on endothelial cell proliferation and tubelike formation. In conclusion, metformin inhibited NADPH oxidase, which in turn suppressed ROS production and NF-κB activation to prevent IL-8 upregulation stimulated by LCA; this prevention thus obstructed endothelial cell proliferation and tubelike formation.
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http://dx.doi.org/10.1038/s41598-019-38778-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376015PMC
February 2019

Effect of anacardic acid against echinococcosis through inhibition of VEGF-induced angiogenesis.

Vet Res 2019 Jan 14;50(1). Epub 2019 Jan 14.

School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.

Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus, with limited treatment options. It is urgent to develop new anti-hydatid agent. In this paper, we reported anacardic acid (AA), a natural product isolated from the Brazilian cashew-nut shell liquid, which presented a high activity against metacestodes of Echinococcus multilocularis (E. multilocularis) and Echinococcus granulosus sensu stricto (E. granulosus s.s.) in vitro and in vivo. AA exerted a better efficacy on E. granulosus s.s. protoscoleces and E. multilocularis metacestodes than that of albendazole (ABZ) and dihydroartemisinin (DHA) in vitro, and an inhibition on the growth of Echinococcus metacestode as effective as ABZ in vivo. Moreover, we also found that one of the mechanisms of AA against Echinococcus could be the suppression of angiogenesis on/in the metacestode mass through inhibiting vascular endothelial growth factor (VEGF)-induced signalling pathways. This work finds that AA is a new promising potential candidate drug for echinococcosis treatment.
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http://dx.doi.org/10.1186/s13567-019-0621-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332641PMC
January 2019

Nicotine stimulates IL-6 expression by activating the AP-1 and STAT-3 pathways in human endothelial EA.hy926 cells.

J Cell Biochem 2019 04 14;120(4):5531-5541. Epub 2018 Oct 14.

Department of Biochemistry, Chonnam National University Medical School, Gwangju, Republic of Korea.

Interleukin-6 (IL-6), a pleiotropic cytokine, plays a key role in endothelial injury and atherosclerosis. In this study, we investigated the effects of nicotine, a major psychoactive compound in cigarette smoke, on IL-6 expression and EA.hy926 endothelial cell invasion. Nicotine stimulated IL-6 expression via the activator protein 1 (AP-1) transcription factor. Pharmacological inhibition and mutagenesis studies indicated that p38 mitogen-activated protein kinase (MAPK) mediated the IL-6-induced upregulation of nicotine in EA.hy926 cells. Furthermore, the antioxidant compound N-acetyl-cysteine eliminated the nicotine-activated production of reactive oxygen species (ROS) and inhibited signal transducer and activator of transcription 3 (STAT-3) phosphorylation; these two mechanisms mediated the upregulation of IL-6 expression by nicotine. In addition, the EA.hy926 cells treated with nicotine displayed markedly enhanced invasiveness due to IL-6 upregulation. Our data demonstrate that nicotine induced IL-6 expression, which, in turn, enhanced the invasiveness of endothelial EA.hy926 cells, via activation of the p38 MAPK/AP-1 and ROS/STAT-3 signaling pathways.
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http://dx.doi.org/10.1002/jcb.27837DOI Listing
April 2019

Analysis of the dissipation kinetics of thiophanate-methyl and its metabolite carbendazim in apple leaves using a modified QuEChERS-UPLC-MS/MS method.

Biomed Chromatogr 2019 Feb 23;33(2):e4394. Epub 2018 Oct 23.

College of Plant Health and Medicine, Qingdao Agricultural University; Key Laboratory of Integrated Crop Pest Management of Shandong Province, Qingdao, China.

As one of the main fungicides for the apple leaf disease control, thiophanate-methyl (TM) mainly exerts its fungicidal activity in the form of its metabolite carbendazim (MBC), whose dissipation kinetics is very distinct from that of its parent but has been paid little attention. The aim of this work was to investigate the dissipation kinetics of TM and its active metabolite MBC in apple leaves using a modified QuEChERS-UPLC-MS/MS method. The results showed that TM and MBC could be quickly extracted by this modified QuEChERS procedure with recoveries of 81.7-96.5%. The method linearity was in the range of 0.01-50.0 mg kg with the quantification limit of 0.01 mg kg . Then this method was applied to the analysis of fungicide dissipation kinetics in apple leaves. The results showed that the dissipation kinetics of TM for the test in 3 months can be described by a first-order kinetics model with a DT (dissipation half-life) range of 5.23-6.03 days and the kinetics for MBC can be described by a first-order absorption-dissipation model with the T (time needed to reach peak concentration) range of 4.78-7.09 days. These models can scientifically describe the behavior of TM and MBC in apple leaves, which provides necessary data for scientific application.
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http://dx.doi.org/10.1002/bmc.4394DOI Listing
February 2019

Effects of Temperature and Moisture on the Infection and Development of Apple Fruit Rot Caused by Phytophthora cactorum.

Plant Dis 2018 Sep 13;102(9):1811-1819. Epub 2018 Jul 13.

College of Plant Health and Medicine, Qingdao Agricultural University; Key Lab of Integrated Crop Pest Management of Shandong Province; Qingdao 266109, P.R. China.

Phytophthora fruit rot, caused by Phytophthora cactorum, is an important disease of apple in China, often causing more than 50% fruit rot in rainy years. We examined the effects of temperature and moisture on the development of the disease and effects of the variables on zoospore release and germination, infection, and lesion development. In vitro, a temperature range of 5 to 20°C had no significant effects on zoospore release dynamics but did significantly affect the quantities of released zoospores. The largest quantity of zoospores was released at 9.9°C according to a fitted model. Zoosporangia released zoospores within 15 min at the test temperatures (0 to 20°C), which peaked at the fourth hour. Zoospores germinated in vitro, requiring free water, at temperatures from 5 to 35°C. The optimum germination temperature was 25.1°C according to a fitted model. The minimum wetness duration required for zoospores to complete the infection process and induce visible lesions on Fuji fruit was 0.40 h at the optimal temperature of 23.0°C according to the fitted model, whereas observed values were 4.5, 1.5, 0.5, 1.5 and 8.5 h at 10, 15, 20, 25, and 30°C, respectively. The number of zoospore infections on fruit at various temperatures and wetness durations were well fitted by the modified Weibull model; based on the model, the optimal temperature for zoospore infections was 23.0°C. Young apple fruit infected by zoospores developed visible lesions from 10 to 30°C, with a predicted optimum of 23.5°C; no lesions developed at 5 or 35°C. The shortest incubation period of the disease was 4 days. These results can be used to develop disease forecasting models for improved fungicide control.
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http://dx.doi.org/10.1094/PDIS-07-17-1028-REDOI Listing
September 2018

Structural characteristics and bioactive properties of a novel polysaccharide from Flammulina velutipes.

Carbohydr Polym 2018 Oct 25;197:147-156. Epub 2018 May 25.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China; Guangdong Provincial Key Laboratory of Biochip, Guangzhou 510515, Guangdong, China. Electronic address:

A new water-soluble polysaccharide (FVP1) was extracted from Flammulina velutipes by traditional method "water extraction and alcohol precipitation" and purified by column chromatography. Physicochemical characterization showed that FVP1 was a homogeneous polysaccharide with a relative molecular weight of 54.78 kDa. It is composed of mannose (7.74%), glucose (70.41%), and galactose (16.38%). FVP1 (1000 mg/mL) possessed significant immune activity by increasing the secretion of nitric oxide (NO), tumour necrosis factor-α (TNF-α) (3183 ± 133.84 pg/mL), interleukin (IL)-6 (1133.21 ± 39.05 pg/mL), and IL-12 (579.96 ± 74.53 pg/mL) in macrophages. Furthermore, FVP1 showed significant hepatitis B surface antibody (anti-HBV) activity through reducing the expression of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA replication. These results suggest a novel role for FVP1 to be applied as an immunomodulators in dietary supplements to prevent HBV infection.
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http://dx.doi.org/10.1016/j.carbpol.2018.05.069DOI Listing
October 2018

Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells.

J Agric Food Chem 2018 Jul 9;66(29):7663-7673. Epub 2018 Jul 9.

Research Institute of Medical Sciences , Chonnam National University Medical School , Gwangju 501-190 , Republic of Korea.

The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a crucial role in cell invasion, and the metastasis of several cancers, including bladder cancer, and its expression are significantly negatively correlated with patient survival rates. Apigenin, a naturally produced phytochemical compound found in fruits, vegetables, and plant leaves, has been shown to mediate a variety of cancer-metastasis-related molecules in various cancers. The effect of apigenin on uPAR expression is still unknown. In this study, we examined the effects of apigenin on IL-1β-induced uPAR expression and investigated its potential mechanisms. We discovered in this study that IL-1β could remarkably induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL-1β could induce uPAR expression concentration-dependently. Interestingly, NF-κB and AP-1 transcription factors were critically required for IL-1β-induced high uPAR expression. Apigenin suppressed the transcriptional activity of both AP-1 and NF-κB by inhibiting ERK1/2 and JNK signaling pathways. These results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-κB signaling pathways in human T24 cells. Our present study generated novel and valuable biological insight into anti-invasion through treatment with a small native compound.
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http://dx.doi.org/10.1021/acs.jafc.8b02351DOI Listing
July 2018

Andrographolide Antagonizes TNF-α-Induced IL-8 via Inhibition of NADPH Oxidase/ROS/NF-κB and Src/MAPKs/AP-1 Axis in Human Colorectal Cancer HCT116 Cells.

J Agric Food Chem 2018 May 14;66(20):5139-5148. Epub 2018 May 14.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences , Southern Medical University , Guangzhou 510515 , Guangdong , China.

Andrographis paniculata Nees is used as a functional food in Japan, Korea, India, and China. Andrographolide, a naturally occurring phytochemical identified in Andrographis paniculata, has been discovered to present anti-inflammatory and anticancer activities. Highly expressed interleukin (IL-8) has been detected in colorectal cancer and is implicated in angiogenesis. However, the effect and molecular mechanisms of IL-8 expression by andrographolide remain obscure in human colorectal cancer cells. The present study was aimed to investigate the effects of andrographolide on TNF-α-induced IL-8 expression and its underlying mechanisms. We found that andrographolide concentration-dependently inhibited TNF-α-induced IL-8 mRNA (2.23 ± 0.15 fold at 20 μM) and protein expression (4.78 ± 0.31 fold at 20 μM) and reduced the IL-8 transcriptional activity (2.59 ± 0.25 fold at 20 μM). TNF-α stimulated the membrane translocation of p47 to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Furthermore, TNF-α induced Src and MAPKs (Erk1/2, p38 MAPK) phosphorylation, as well as NF-κB and AP-1 binding activities. We found that NF-κB and AP-1 were the critical transcription factors for TNF-α-induced IL-8 expression. Specific inhibitors and mutagenesis studies indicated that Src, Erk1/2, and p38 MAPK are related to TNF-α-induced IL-8. NOX-derived ROS and Src/MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. Taken together, andrographolide antagonizes TNF-α-induced IL-8 via inhibition of NADPH oxidase/ROS/NF-κB and Src/MAPKs/AP-1 signaling pathways in HCT116 colorectal cancer cells and then suppresses angiogenesis in the tumor microenvironment.
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http://dx.doi.org/10.1021/acs.jafc.8b00810DOI Listing
May 2018

Peach RNA viromes in six different peach cultivars.

Sci Rep 2018 01 30;8(1):1844. Epub 2018 Jan 30.

Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

Many recent studies have demonstrated that several known and unknown viruses infect many horticultural plants. However, the elucidation of a viral population and the understanding of the genetic complexity of viral genomes in a single plant are rarely reported. Here, we conducted metatranscriptome analyses using six different peach trees representing six individual peach cultivars. We identified six viruses including five viruses in the family Betaflexiviridae and a novel virus belonging to the family Tymoviridae as well as two viroids. The number of identified viruses and viroids in each transcriptome ranged from one to six. We obtained 18 complete or nearly complete genomes for six viruses and two viroids using transcriptome data. Furthermore, we analyzed single nucleotide variations for individual viral genomes. In addition, we analyzed the amount of viral RNA and copy number for identified viruses and viroids. Some viruses or viroids were commonly present in different cultivars; however, the list of infected viruses and viroids in each cultivar was different. Taken together, our study reveals the viral population in a single peach tree and a comprehensive overview for the diversities of viral communities in different peach cultivars.
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http://dx.doi.org/10.1038/s41598-018-20256-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789896PMC
January 2018

Study of formation of green eggshell color in ducks through global gene expression.

PLoS One 2018 29;13(1):e0191564. Epub 2018 Jan 29.

College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou, Fujian, People's Republic of China.

The green eggshell color produced by ducks is a threshold trait that can be influenced by various factors, such as hereditary, environment and nutrition. The aim of this study was to investigate the genetic regulation of the formation of eggs with green shells in Youxian ducks. We performed integrative analysis of mRNAs and miRNAs expression profiling in the shell gland samples from ducks by RNA-Seq. We found 124 differentially expressed genes that were associated with various pathways, such as the ATP-binding cassette (ABC) transporter and solute carrier supper family pathways. A total of 31 differentially expressed miRNAs were found between ducks laying green eggs and white eggs. KEGG pathway analysis of the predicted miRNA target genes also indicated the functional characteristics of these miRNAs; they were involved in the ABC transporter pathway and the solute carrier (SLC) supper family. Analysis with qRT-PCR was applied to validate the results of global gene expression, which showed a correlation between results obtained by RNA-seq and RT-qPCR. Moreover, a miRNA-mRNA interaction network was established using correlation analysis of differentially expressed mRNA and miRNA. Compared to ducks that lay white eggs, ducks that lay green eggs include six up-regulated miRNAs that had regulatory effects on 35 down-regulated genes, and seven down-regulated miRNAs which influenced 46 up-regulated genes. For example, the ABC transporter pathway could be regulated by expressing gga-miR-144-3p (up-regulated) with ABCG2 (up-regulated) and other miRNAs and genes. This study provides valuable information about mRNA and miRNA regulation in duck shell gland tissues, and provides foundational information for further study on the eggshell color formation and marker-assisted selection for Youxian duck breeding.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191564PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788541PMC
March 2018

Genome Sequence of Grapevine Virus T, a Novel Foveavirus Infecting Grapevine.

Genome Announc 2017 Sep 14;5(37). Epub 2017 Sep 14.

Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea

Here, we report the genome sequence of grapevine virus T (GVT), a novel single-stranded RNA virus identified from a transcriptome of grapevine. The genome of GVT is 8,701 nucleotides in length and encodes five open reading frames. GVT is a putative member of the genus in the family .
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http://dx.doi.org/10.1128/genomeA.00995-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597771PMC
September 2017

Genome Sequence of Grapevine Virus K, a Novel Vitivirus Infecting Grapevine.

Genome Announc 2017 Sep 14;5(37). Epub 2017 Sep 14.

Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea

Here, we report the genome sequence of grapevine virus K (GVK), a novel single-stranded RNA virus identified from a transcriptome of grapevine. The genome of GVK is 7,476 nucleotides in length and encodes 5 open reading frames. GVK is a putative member of the genus in the family .
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http://dx.doi.org/10.1128/genomeA.00994-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597770PMC
September 2017

Identification of residues or motif(s) of the rice stripe virus NS3 protein required for self-interaction and for silencing suppressor activity.

Virus Res 2017 05 6;235:14-23. Epub 2017 Apr 6.

Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, and Plant Genomics and Breeding Institute, College of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:

Rice stripe virus (RSV) is an important pathogen of rice. The RSV genome consists of four single-stranded RNA segments that encode seven viral proteins. A previous report found that NS3 is a viral suppressor of RNA silencing and self interacts. Using a model that predicts protein structure, we identified amino acid residues or motifs, including four α-helix motifs, required for NS3 self-interaction. We then used yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays to study the interactions between full-length NS3 and its truncated and alanine substitution mutants. Y2H and BiFC results showed that the N-terminal region of NS3 is essential for self-interaction. All α-helix deletion mutants and substitution mutants lost the ability to self-interact. To identify the relationship between NS3 self-interaction and silencing suppressor activity, we used a GFP silencing system in Nicotiana benthamiana with Agrobacterium-mediated transient overexpression of each mutated NS3 protein. All of the deletion and the α-helix substitution mutants that had lost the ability to self-interact also lost their silencing suppressor ability. The substitution of amino acids with alanine at positions 70-75, 76-83, and 173-177, however, resulted in mutants that were able to self-interact but were unable to function as silencing suppressors. These results suggest that RSV requires NS3 self-interaction to suppress RNA silencing and to thereby counter host defenses.
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http://dx.doi.org/10.1016/j.virusres.2017.03.022DOI Listing
May 2017

Effects of Temperature and Moisture on Sporulation and Infection by Pseudoperonospora cubensis.

Plant Dis 2017 Apr 19;101(4):562-567. Epub 2017 Jan 19.

Key Lab of Integrated Crop Pests Management of Shandong Province, Qingdao, Shandong 266109, P. R. China and College of Crop Protection and Agronomy, Qingdao Agricultural University, Qingdao 266109, P. R. China.

Cucumber downy mildew, caused by Pseudoperonospora cubensis, is a worldwide disease that causes severe damage to cucumber production. The effects of temperature and moisture on sporulation and infection by P. cubensis were investigated by inoculating cucumber ('85F12') cotyledons with sporangia and examining the sporangia produced on the inoculated cotyledons under artificially controlled environments. The result showed that the temperature required for sporangium infection by P. cubensis and sporulation of the downy mildew lesions occurred at 5 to 30°C. The optimal temperature estimated by the fitted model was 18.8°C for sporangium infection and 16.2°C for downy mildew lesion sporulation. The pathogen formed plenty of sporangia when disease cotyledons were wetted or in the environment with relative humidity = 100%. The downy mildew lesions produced only a few sporangia when placed in the environment with relative humidity = 90%. The inoculated cotyledons, which incubated for 5 days at about 20°C in a dry greenhouse, began to form sporangia 4 h after being wetted when incubated in darkness. The quantity of sporangia produced on the downy mildew lesions increased with extension of incubating period (within 12 h), and the relationship between produced sporangia and the incubation period at 15, 20, and 25°C can be described by three exponential models. The observed minimum wetness durations (MWD) required for sporangia to complete the infection process and cause downy mildew were 12, 4, 2.5, 1, 1, and 6 h for 5, 10, 15, 20, 25, and 30°C, respectively. The effect of temperature and wetness duration on infection by sporangia of P. cubensis can be described by the modified Weibull model. The shortest MWD was 0.45 h, about 27 min, estimated by model. The experimental data and models will be helpful in the development of forecasting models and effective control systems for cucumber downy mildew.
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http://dx.doi.org/10.1094/PDIS-09-16-1232-REDOI Listing
April 2017

Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells Via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity.

J Cell Biochem 2017 09 3;118(9):2958-2967. Epub 2017 May 3.

Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.

The secondary bile acid lithocholic acid (LCA), an established tumor promoter, has been implicated in colorectal cancer (CRC) metastasis. Overexpression of interleukin-8 (IL-8) has been detected in CRC, and it contributes to poor prognosis. However, the effect of LCA on IL-8 expression is still undefined. In this study, we observed that LCA treatment induced IL-8 expression in CRC HCT116 cells. Pharmacological inhibition and mutagenesis studies indicated that Erk1/2 is critical for LCA-induced IL-8 expression. Furthermore, LCA reduced the phosphorylation of STAT3, and the STAT3 inhibitor Stattic, accelerated LCA-induced IL-8 expression, suggesting that STAT3 is involved in LCA-induced IL-8 expression. Activation of Erk1/2 functioned as an upstream signal of the STAT3 suppression induced by LCA. In conclusion, LCA activated Erk1/2 and in turn, suppressed STAT3 phosphorylation to induce IL-8 expression in HCT116 cells, thus stimulating endothelial cell proliferation and tube like formation. J. Cell. Biochem. 118: 2958-2967, 2017. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jcb.25955DOI Listing
September 2017

Effects of Temperature, Humidity, and Wound Age on Valsa mali Infection of Apple Shoot Pruning Wounds.

Plant Dis 2016 Dec 15;100(12):2394-2401. Epub 2016 Sep 15.

College of Crop Protection and Agronomy, Qingdao Agricultural University, Key Lab of Integrated Crop Pests Management of Shandong Province, Qingdao, Shandong 266109, P. R. China.

Valsa canker, caused by Valsa mali, is a destructive disease of apple in China. The pathogen infects apple branches, mainly through pruning wounds, and causes branch and tree death. To determine the conditions required for V. mali infection through pruning wounds and growth within the xylem, pruning wounds on 1- to 4-year-old apple branches were inoculated with conidia in vitro under artificially controlled conditions and in vivo in the orchard. The effects of temperature, wetness duration, and wound age on conidial infection through pruning wounds as well as hyphal growth in the xylem were examined. The results showed that, after invading through pruning wounds, V. mali hyphae grew along xylem vessels, tracheids, and rays, expanding longitudinally and laterally. The hyphae could enter adjacent xylem vessels and tracheids through micropores to form a dense hyphal network. Wetness duration did not exhibit an essential effect on conidial infection from pruning wounds. Conidia spread to pruning wounds with rainwater could infect the xylem without any other extra moisture. Temperature for V. mali conidia infection through pruning wounds and hyphal extension in the xylem ranged from 5 to 35°C, with the optimum at 20°C. Pruning wounds made in late March were susceptible to V. mali infection in March, April, and May; the susceptibility was markedly deceased by June, and the pathogen could barely infect through the pruning wounds in November. The infected pruning wounds began to show symptoms from the spring of the following year. More than half of the observed Valsa canker lesions emerged in the spring of the second year, and new canker twigs were also developed from the inoculations in the spring of the third year. March, April, and May are the critical periods for protecting pruning wounds against infection by V. mali in China, and coating pruning wounds with protective film immediately after pruning is an easy and effective measure to protect the pruning wounds.
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http://dx.doi.org/10.1094/PDIS-05-16-0625-REDOI Listing
December 2016

Draft Genome Sequence of Botryosphaeria dothidea, the Pathogen of Apple Ring Rot.

Genome Announc 2016 Oct 27;4(5). Epub 2016 Oct 27.

College of Crop Protection and Agronomy, Qingdao Agricultural University, and Key Lab of Integrated Crop Pests Management of Shandong Province, Qingdao, Shandong, People's Republic of China.

Botryosphaeria dothidea is a destructive pathogen infecting apple (Malus domestica) on the fruit and stem. Here, we present the draft genome sequence of B. dothidea (strain LW030101) using Illumina sequencing. The draft genome sequence provides useful information and acts as a platform for further research on the pathogen.
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http://dx.doi.org/10.1128/genomeA.01142-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084859PMC
October 2016

MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d'Origine Nantais.

Int J Mol Sci 2016 Sep 27;17(10). Epub 2016 Sep 27.

Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190 Gwangju, Korea.

Emerging evidence supports a fundamental role for microRNAs (miRNA) in regulating cancer metastasis. Recently, () was reported to be downregulated in many types of cancers, including gastric cancer. Increase in the expression of Recepteur d'Origine Nantais (RON), a receptor tyrosine kinase, has been reported in tumors. However, the function of and RON expression in gastric cancer metastasis has not been sufficiently studied. In silico analysis identified binding sites in the 3'-untranslated regions (3'-UTR) of the RON-encoding gene. Expression of resulted in reduced activity of a luciferase reporter containing the 3'-UTR fragments of RON-encoding mRNA, confirming that directly targets the 3'-UTR of RON mRNA. Moreover, we found that overexpression of inhibited mRNA and protein expression of RON, which was accompanied by the suppression of cell proliferation, migration, and invasion in gastric cancer AGS and MKN-28 cells. Ectopic expression also induced G1 cell cycle arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of retinoblastoma (Rb). Knockdown of RON by RNAi, similar to overexpression, suppressed tumorigenic properties and induced G1 arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of Rb. Thus, our study provides evidence that acts as a suppressor of metastasis in gastric cancer by targeting RON, and might represent a new potential therapeutic target for gastric cancer.
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http://dx.doi.org/10.3390/ijms17101633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085666PMC
September 2016
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