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      • KCI등재

        Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis

        Jiani Yi,Mengting Wu,Zhihong Zheng,Qing Zhou,Xufan Li,Yan Lu,Pengyuan Liu 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.6

        Objective: More than 75% of ovarian cancer patients are diagnosed at advanced stages and die of tumor cell metastasis. This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis. Methods: Two cell sublines with low- and high-metastasis potentials were derived from the ovarian cancer cell line A2780. Genome-wide DNA methylome and transcriptome profiling were carried out in these two sublines by Reduced Representation Bisulfite Sequencing and RNA-seq technologies. Cell-based assays were conducted to support the clinical findings. Results: There are distinct DNA methylation and gene expression patterns between the two cell sublines with low- and high-metastasis potentials. Integrated analysis identified 33 methylation-induced genes potentially involved in ovarian cancer metastasis. The DNA methylation patterns of two of them (i.e., SFRP1 and LIPG) were further validated in human specimens, indicating that they were hypermethylated and downregulated in peritoneal metastatic ovarian carcinoma compared to primary ovarian carcinoma. Patients with lower SFRP1 and LIPG expression tend to have a worse prognosis. Functionally, knockdown of SFRP1 and LIPG promoted cell growth and migration, whereas their overexpression resulted in the opposite effects. In particular, knockdown of SFRP1 could phosphorylate GSK3β and increase β-catenin expression, leading to deregulated activation of the Wnt/β-catenin signaling. Conclusion: Many systemic and important epigenetic and transcriptomic alterations occur in the progression of ovarian cancer. In particular, epigenetic silencing of SFRP1 and LIPG is a potential driver event in ovarian cancer metastasis. They can be used as prognostic biomarkers and therapeutic targets for ovarian cancer patients.

      • KCI등재

        Anti-colonic Inflammation by Black Raspberries through Regulating Toll-like Receptor-4 Signaling in Interlukin-10 Knockout Mice

        Yi-Wen Huang,Carla Elena Echeveste,Kiyoko Oshima,Jianying Zhang,Martha Yearsley,Jianhua Yu,Li-Shu Wang 대한암예방학회 2020 Journal of cancer prevention Vol.25 No.2

        Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, with a steadily rising prevalence in Western and newly industrialized countries. UC patients have a cancer incidence as high as 10% after 20 years of the disease. Although the importance of fruits and vegetables in defense against UC is beginning to be appreciated, the mechanisms remain largely unclear. In the current study, we reported that dietary black raspberries (BRBs) decreased colonic inflammation in the mucosa and submucosa of interleukin (IL)-10 knockout (KO) mice. We then used colon, spleen, and plasma from those mice to investigate whether BRBs exert their anti-inflammatory effects by correcting dysregulated toll-like receptor (TLR)-4 signaling to downregulate prostaglandin E2 (PGE2). Other studies reported that spleen is the reservoir of macrophages and depletion of macrophages in IL-10 KO mice prevents the development of colitis. Our results showed that BRBs decreased the percentages of macrophages in spleens of IL-10 KO mice. Moreover, mechanistically, the BRB diet corrected dysregulated TLR-4 signaling in cells from the colon and spleen, decreased PGE2 and prostaglandin I2, and increased 15-lipoxygenase and its product, 13-S-hydroxyoctadecadienoic acid, in plasma of IL- 10 KO mice. Therefore, we have elucidated one of the anti-inflammatory mechanisms of BRBs, and have identified biomarkers that could be indicators of response in UC patients treated with them. Our findings with BRBs could well apply to many other commonly consumed fruits and vegetables.

      • SCISCIESCOPUS

        Naphthenic Acids in Coastal Sediments after the <i>Hebei Spirit</i> Oil Spill: A Potential Indicator for Oil Contamination

        Wan, Yi,Wang, Beili,Khim, Jong Seong,Hong, Seongjin,Shim, Won Joon,Hu, Jianying American Chemical Society 2014 Environmental science & technology Vol.48 No.7

        <P>Naphthenic acids (NAs) as toxic components in most petroleum sources are suspected to be one of the major pollutants in the aquatic environment following oil spills, and the polarity and persistence of NAs make it a potential indicator for oil contamination. However, the contamination and potential effects of pollutants in oil spill affected areas remain unknown. To investigate NAs in oil spill affected areas, a sensitive method was first established for analysis of NAs, together with oxy-NAs in sediment samples by UPLC-QTOF-MS. Then the method was applied to determine the NA mixtures in crude oil, weathered oil, and sediments from the spilled sites after the <I>Hebei Spirit</I> oil spill, Taean, South Korea (Dec. 2007). Concentrations of NAs, O<SUB>3</SUB>–NAs, and O<SUB>4</SUB>–NAs were found to be 7.8–130, 3.6–44, and 0.8–20 mg kg<SUP>–1</SUP> dw in sediments from the Taean area, respectively, which were much greater than those measured in the reference sites of Manlipo and Anmyundo beaches. Concentrations of NAs were 50–100 times greater than those (0.077–2.5 mg kg<SUP>–1</SUP> dw) of PAHs in the same sediment samples, thus the ecological risk of NAs in oil spill affected areas deserves more attention. The sedimentary profiles of oil-derived NAs and background NAs centered around compounds with 21–35 and 12–21 carbons, respectively, indicating that the crude-derived NA mixtures originating from the 2007 oil spill were persistent. Acyclic NAs<SUB><I>n</I>=5–20</SUB> were easily degraded compared to cyclic NAs<SUB><I>n</I>=21–41</SUB> during the oil weathering processes, and the ratio of oxy-NAs<SUB><I>n</I>=21–41</SUB> relative to NAs<SUB><I>n</I>=21–41</SUB> could be a novel index to estimate the degree of oil weathering in sediments. Altogether, the persistent oil-derived NAs<SUB><I>n</I>=21–41</SUB> could be used as a potential indicator for oil-specific contamination, as such compounds would not be much affected by the properties of coastal sediments possibly due to the high sorption of the negatively charged compounds (NAs) in sediment.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/esthag/2014/esthag.2014.48.issue-7/es405034y/production/images/medium/es-2013-05034y_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/es405034y'>ACS Electronic Supporting Info</A></P>

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