http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Cong Weixuan,Li Ning,Wang Jinbin,Kang Ying,Miao Yiling,Xu Chunming,Wang Ziqi,Liu Tongtong,Gong Lei,Liu Bao,Ou Xiufang 한국유전학회 2022 Genes & Genomics Vol.44 No.3
Background: Albeit a relatively stable epigenetic modification, DNA methylation in plants can be repatterned and play important roles in response to biotic and abiotic stresses. However, whether DNA methylation dynamics may contribute to cope with mercury (Hg) stress in plants remains to be fully investigated. Objective: To probe the potential roles of DNA methylation dynamics in coping with Hg stress in rice. Methods: Whole-genome bisulfite sequencing was used to profile the DNA methylation patterns of a rice Hg-resistant line (RHg) selected from a heterozygous mutant of the DNA methyltransferase 1 gene (OsMET1+/-), together with its Hg-sensitive wild-type plants of cv. Nipponbare (Nip) under both normal and Hg stress conditions. Results: Genome-wide locus-specific differential methylation regions (DMRs) were detected between RHg and Nip under normal condition, the predominant DMR patterns were CG hypo-DMRs, CHG hypo-DMRs and CHH hyper-DMRs. In both lines, more hyper- than hypo-DMRs were detected at all three sequence contexts (CG, CHG and CHH) under Hg stress relative to normal condition. Comparison of DNA methylation changes in the two lines under Hg stress indicates that RHg had a more dynamic methylome than the control (Nip). Original DMRs in RHg trended to transform to opposite status (from hyper- to hypo- or vice versa) under Hg stress condition. Gene ontology analysis revealed that Hg-resistance-related DMGs were enriched in diverse biological processes. Conclusions: Our results suggest genome-wide locus-specific DNA methylation repatterning can facilitate rapid acquisition of Hg resistance in rice.
Wang, Chao,Gu, Chao,Jeong, Kang Jin,Zhang, Dong,Guo, Wei,Lu, Yiling,Ju, Zhenlin,Panupinthu, Nattapon,Yang, Ji Yeon,Gagea, Mihai (Mike),Ng, Patrick Kwok Shing,Zhang, Fan,Mills, Gordon B. American Association for Cancer Research 2017 Cancer Research Vol.77 No.7
<P>Interactions between HIPPO, YAP/TAZ, and the PI3K/AKT pathway may be therapeutically targetable, providing new approaches to treating endometrial cancers and other cancers where the HIPPO pathway is a core oncogenic driver.</P><P>The transcription regulators YAP and TAZ function as effectors of the HIPPO signaling cascade, critical for organismal development, cell growth, and cellular reprogramming, and YAP/TAZ is commonly misregulated in human cancers. The precise mechanism by which aberrant YAP/TAZ promotes tumor growth remains unclear. The HIPPO tumor suppressor pathway phosphorylates YAP and TAZ, resulting in cytosolic sequestration with subsequent degradation. Here, we report that the PI3K/AKT pathway, which is critically involved in the pathophysiology of endometrial cancer, interacts with the HIPPO pathway at multiple levels. Strikingly, coordinate knockdown of YAP and TAZ, mimicking activation of the HIPPO pathway, markedly decreased both constitutive and growth factor–induced PI3K pathway activation by decreasing levels of the GAB2 linker molecule in endometrial cancer lines. Furthermore, targeting YAP/TAZ decreased endometrial cancer tumor growth <I>in vivo</I>. In addition, YAP and TAZ total and phosphoprotein levels correlated with clinical characteristics and outcomes in endometrial cancer. Thus, YAP and TAZ, which are inhibited by the HIPPO tumor suppressor pathway, modify PI3K/AKT pathway signaling in endometrial cancer. The cross-talk between these key pathways identifies potential new biomarkers and therapeutic targets in endometrial cancer. <I>Cancer Res; 77(7); 1637–48. ©2017 AACR</I>.</P>
Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers
Wang, Yumeng,Xu, Xiaoyan,Yu, Shuangxing,Jeong, Kang Jin,Zhou, Zhicheng,Han, Leng,Tsang, Yiu Huen,Li, Jun,Chen, Hu,Mangala, Lingegowda S.,Yuan, Yuan,Eterovic, A. Karina,Lu, Yiling,Sood, Anil K.,Scott, Cold Spring Harbor Laboratory Press 2017 Genome research Vol.27 No.7
<P>RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit <I>ZEB1/ZEB2</I> and acquired concomitant ability to repress new targets, including <I>LIFR</I>, a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy.</P>
Sun, Chaoyang,Yin, Jun,Fang, Yong,Chen, Jian,Jeong, Kang Jin,Chen, Xiaohua,Vellano, Christopher P.,Ju, Zhenlin,Zhao, Wei,Zhang, Dong,Lu, Yiling,Meric-Bernstam, Funda,Yap, Timothy A.,Hattersley, Mauree Cell Press 2018 CANCER CELL Vol. No.
<P><B>Summary</B></P> <P>Poly(ADP-ribose) polymerase inhibitors (PARPi) are selectively active in cells with homologous recombination (HR) deficiency (HRD) caused by mutations in <I>BRCA1</I>, <I>BRCA2</I>, and other pathway members. We sought small molecules that induce HRD in HR-competent cells to induce synthetic lethality with PARPi and extend the utility of PARPi. We demonstrated that inhibition of bromodomain containing 4 (BRD4) induced HRD and sensitized cells across multiple tumor lineages to PARPi regardless of <I>BRCA1/2</I>, <I>TP53</I>, <I>RAS</I>, or <I>BRAF</I> mutation status through depletion of the DNA double-stand break resection protein CtIP (C-terminal binding protein interacting protein). Importantly, BRD4 inhibitor (BRD4i) treatment reversed multiple mechanisms of resistance to PARPi. Furthermore, PARPi and BRD4i are synergistic in multiple <I>in vivo</I> models.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BRD4 inhibition decreases homologous recombination competency by decreasing CtIP </LI> <LI> PARP and BRD4 inhibitors demonstrate synergy in multiple cancer lineages </LI> <LI> CtIP rescues DNA end resection and HR defect caused by BRD4 inhibition </LI> <LI> BRD4 inhibition resensitizes cells with acquired PARPi resistance to PARPi </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
A-to-I RNA Editing Contributes to Proteomic Diversity in Cancer
Peng, Xinxin,Xu, Xiaoyan,Wang, Yumeng,Hawke, David H.,Yu, Shuangxing,Han, Leng,Zhou, Zhicheng,Mojumdar, Kamalika,Jeong, Kang Jin,Labrie, Marilyne,Tsang, Yiu Huen,Zhang, Minying,Lu, Yiling,Hwu, Patrick Cell Press 2018 CANCER CELL Vol. No.
Sun, Chaoyang,Fang, Yong,Yin, Jun,Chen, Jian,Ju, Zhenlin,Zhang, Dong,Chen, Xiaohua,Vellano, Christopher P.,Jeong, Kang Jin,Ng, Patrick Kwok-Shing,Eterovic, Agda Karina B.,Bhola, Neil H.,Lu, Yiling,Wes American Association for the Advancement of Scienc 2017 Science translational medicine Vol.9 No.392
<P>Mutant <I>RAS</I> has remained recalcitrant to targeted therapy efforts. We demonstrate that combined treatment with poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors and mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors evokes unanticipated, synergistic cytotoxic effects in vitro and in vivo in multiple <I>RAS</I> mutant tumor models across tumor lineages where <I>RAS</I> mutations are prevalent. The effects of PARP and MEK inhibitor combinations are independent of <I>BRCA1/2</I> and <I>p53</I> mutation status, suggesting that the synergistic activity is likely to be generalizable. Synergistic activity of PARP and MEK inhibitor combinations in <I>RAS</I> mutant tumors is associated with (i) induction of BIM-mediated apoptosis, (ii) decrease in expression of components of the homologous recombination DNA repair pathway, (iii) decrease in homologous recombination DNA damage repair capacity, (iv) decrease in DNA damage checkpoint activity, (v) increase in PARP inhibitor–induced DNA damage, (vi) decrease in vascularity that could increase PARP inhibitor efficacy by inducing hypoxia, and (vii) elevated PARP1 protein, which increases trapping activity of PARP inhibitors. Mechanistically, enforced expression of FOXO3a, which is a target of the RAS/MAPK pathway, was sufficient to recapitulate the functional consequences of MEK inhibitors including synergy with PARP inhibitors. Thus, the ability of mutant <I>RAS</I> to suppress FOXO3a and its reversal by MEK inhibitors accounts, at least in part, for the synergy of PARP and MEK inhibitors in <I>RAS</I> mutant tumors. The rational combination of PARP and MEK inhibitors warrants clinical investigation in patients with <I>RAS</I> mutant tumors where there are few effective therapeutic options.</P>
김무강,Mi-SunPark,Mi-YoungLee,Keun-JwaLee,Young-GilJeong,Chul-HoLee,Kwon-SooHa,Man-HeeRhee,Kang-YiLee,Kyoug-YoulLee,Chi-WonSong,권효정 대한수의학회 2002 Journal of Veterinary Science Vol.3 No.3
The distribution of the nerve growth factor (NGF),the glial fibrillary acidic protein (GFAP) and theciliary neurotrohic factor (CNTF) was performed incoronal sections of the mesencephalon, rhombencephalonand spinal cord in the developing Mongolian gerbils.Generaly, NGF specificaly recognizes neurons withthe NGF receptor, whereas GFAP does the glia, andwas examined separately in gerbils between embryonicdays 15 (E15) and postnatal weks 3 (PNW 3). TheNGF-IR was first observed in the spinal cord at E21,which might be related to the maturation. The GFAPreactivity was peaked at he postnatal days 2 (PND2),while the highest CNTF-reaction was expresed atPNW 2. The GFAP stains were observed in theaqueduct and the spinal cord, which appeared toproject lateraly at E19. The CNTF was observed onlyafter the birth and found in both the neurons andcerebelum and the spinal cord from PND1 to PNW3.These results uggest hat NGF, GFAP and CNTF areimportant for the development of the neurons and theneuroglia in the central nervous system at he lateprenatal and postnatal stages.