@article{SongJiaZhangetal.2016, author = {Song, Ning-Ning and Jia, Yun-Fang and Zhang, Lei and Zhang, Qiong and Huang, Ying and Liu, Xiao-Zhen and Hu, Ling and Lan, Wei and Chen, Ling and Lesch, Klaus-Peter and Chen, Xiaoyan and Xu, Lin and Ding, Yu-Qiang}, title = {Reducing central serotonin in adulthood promotes hippocampal neurogenesis}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, number = {20338}, doi = {10.1038/srep20338}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168004}, year = {2016}, abstract = {Chronic administration of selective serotonin reuptake inhibitors (SSRIs), which up-regulates central serotonin (5-HT) system function, enhances adult hippocampal neurogenesis. However, the relationship between central 5-HT system and adult neurogenesis has not fully been understood. Here, we report that lowering 5-HT level in adulthood is also able to enhance adult hippocampal neurogenesis. We used tamoxifen (TM)-induced Cre in Pet1-CreER\(^{T2}\) mice to either deplete central serotonergic (5-HTergic) neurons or inactivate 5-HT synthesis in adulthood and explore the role of central 5-HT in adult hippocampal neurogenesis. A dramatic increase in hippocampal neurogenesis is present in these two central 5-HT-deficient mice and it is largely prevented by administration of agonist for 5-HTR2c receptor. In addition, the survival of new-born neurons in the hippocampus is enhanced. Furthermore, the adult 5-HT-deficient mice showed reduced depression-like behaviors but enhanced contextual fear memory. These findings demonstrate that lowering central 5-HT function in adulthood can also enhance adult hippocampal neurogenesis, thus revealing a new aspect of central 5-HT in regulating adult neurogenesis.}, language = {en} } @article{ShiKuaiLeietal.2016, author = {Shi, Yaoyao and Kuai, Yue and Lei, Lizhen and Weng, Yuanyuan and Berberich-Siebelt, Friederike and Zhang, Xinxia and Wang, Jinjie and Zhou, Yuan and Jiang, Xin and Ren, Guoping and Pan, Hongyang and Mao, Zhengrong and Zhou, Ren}, title = {The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma}, series = {Oncotarget}, volume = {7}, journal = {Oncotarget}, number = {47}, doi = {10.18632/oncotarget.12680}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166500}, pages = {77444-77456}, year = {2016}, abstract = {Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5\% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6. Therefore, we sought to explore the feedback loop between LITAF and BCL6 in B-NHL. Here, our data for the first time show that LITAF can repress expression of BCL6 by binding to Region A (-87 to +65) containing a putative LITAF-binding motif (CTCCC) within the BCL6 promoter. Furthermore, the regulation of BCL6 targets (PRDM1 or c-Myc) by LITAF may be associated with B-cell differentiation. Results also demonstrate that ectopic expression of LITAF induces cell apoptosis, activated by releasing cytochrome c, cleaving PARP and caspase 3 in B-NHL cells whereas knockdown of LITAF robustly protected cells from apoptosis. Interestingly, BCL6, in turn, could reverse cell apoptosis mediated by LITAF. Collectively, our findings provide a novel apoptotic regulatory pathway in which LITAF, as a transcription factor, inhibits the expression of BCL6, which leads to activation of the intrinsic mitochondrial pathway and tumor apoptosis. Our study is expected to provide a possible biomarker as well as a target for clinical therapies to promote tumor cell apoptosis.}, language = {en} } @article{SongXiuHuangetal.2011, author = {Song, Ning-Ning and Xiu, Jian-Bo and Huang, Ying and Chen, Jia-Yin and Zhang, Lei and Gutknecht, Lise and Lesch, Klaus Peter and Li, He and Ding, Yu-Qiang}, title = {Adult Raphe-Specific Deletion of Lmx1b Leads to Central Serotonin Deficiency}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0015998}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133581}, pages = {e15998}, year = {2011}, abstract = {The transcription factor Lmx1b is essential for the differentiation and survival of central serotonergic (5-HTergic) neurons during embryonic development. However, the role of Lmx1b in adult 5-HTergic neurons is unknown. We used an inducible Cre-LoxP system to selectively inactivate Lmx1b expression in the raphe nuclei of adult mice. Pet1-CreER(T2) mice were generated and crossed with Lmx1b(flox/flox) mice to obtain Pet1-CreER(T2); Lmx1b(flox/flox) mice (which termed as Lmx1b iCKO). After administration of tamoxifen, the level of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60\% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-regulated. On the other hand, the expression of dopamine and norepinephrine as well as aromatic L-amino acid decarboxylase (Aadc) and Pet1 was unchanged. Our results reveal that Lmx1b is required for the biosynthesis of 5-HT in adult mouse brain, and it may be involved in maintaining normal functions of central 5-HTergic neurons by regulating the expression of Tph2, Sert and Vmat2.}, language = {en} } @article{KuaiGongDingetal.2018, author = {Kuai, Yue and Gong, Xin and Ding, Liya and Li, Fang and Lei, Lizhen and Gong, Yuqi and Liu, Qingmeng and Tan, Huajiao and Zhang, Xinxia and Liu, Dongyu and Ren, Guoping and Pan, Hongyang and Shi, Yaoyao and Berberich-Siebelt, Friederike and Ma, Zhengrong and Zhou, Ren}, title = {Wilms' tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90}, series = {Cell Communication and Signaling}, volume = {16}, journal = {Cell Communication and Signaling}, doi = {10.1186/s12964-018-0258-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230168}, year = {2018}, abstract = {Background Wilms' tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear. Methods Immunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation. Results WTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro. Conclusion WTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL.}, language = {en} }