董培新

董 培新（ドン バイシン; Dong Peixin）は、日本の癌研究者、医学博士。北海道大学医学部。

**略歴**
 1997年6月 中国ハルビン医科大学卒業- 1997年8月 中国ハルビン医科大学付属黒龍江省電力病院婦人科医員- 2002年10月 福岡大学医学部産婦人科研究員- 2004年4月 北海道大学大学院医学研究科婦人科専攻入学- 2008年3月 北海道大学大学院医学研究科婦人科専攻終了(博士号取得)- 2008年4月 中国上海復旦大学付属病院産婦人科病院助手- 2009年4月 中国上海復旦大学付属病院産婦人科病院講師- 2010年4月 北海道大学医学研究科産婦人科学分野

**受賞歴**
 2011年度 北海道産科婦人科学会賞（October 28, 2012）受賞- 2015年度 北海道大学研究総長賞（February 3, 2016）受賞

**所属学会**
  日本産婦人科学会（会員：2011年～現在）
*北海道産婦人科学会（会員：2011年～現在）-  日本RNA学会（会員：2014年～現在）

**社会における活動**
国際誌Editorial Board Member：- Journal of Cancer Research & Therapy、2013年～2015年- Cancer Growth and Metastasis、2013年～2015年- Austin Journal of Women’s Health、2014年～現在- Women's Health Research、2017～現在
国際誌reviewer：-  Oncotarget-  Scientific Reports- Journal of Translational Medicine- Gynecologic Oncology- BMC Cancer-  Journal of Experimental & Clinical Cancer Research- FEBS Letters- Molecular and cellular biochemistry- International Journal of Gynecology & Obstetrics

**専攻分野**
  癌転移-  婦人科癌; endometrial carcinoma; cervical cancer; ovarian cancer- microRNA- EMT: epithelial to mesenchymal transition (EMT)-  Twist1 gene, a critical EMT inducer in endometrial cancer- :en:Cervical_cancer cervical cancer- p53: TP53, tumor suppressor in human tumors- endometrial cancer- ovarian cancer-  miR-194 is a tumor suppressor in endometrial cancer-  Prognostic significance of miR-194 in endometrial cancer-  miR-130b in endometrial cancer-  miR-101 is key tumor suppressor in both type I and type II endometrial cancer-  IQGAP1 is novel oncogene in endometrial cancer and ovarian cancer-  miR-106b acts as tumor suppressor in aggressive in endometrial cancer-  KLF17 gene induces EMT in endometrial cancer-  miR-31 functions as an oncogene by suppressing Hippo tumor suppressor pathway in endometrial cancer-  MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells. 35, Article number: 132 (2016)-  iASPP and p53 in human tumors-  miRNA-mediated PI3K/AKT signaling in endometrial cancer-  miRNA-124 directly targets and inhibits IQGAP1 expression in endometrial cancer-  EZH2 induces Twist expression by repressing miR-361 expression in aggressive type II endometrial cancer-  CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells-  lentiviral CRISPR/Cas9-mediated disruption of miR-21 inhibits EMT in ovarian cancer cells-  miR-124 binds to and suppresses oncogene iASPP expression in cervical cancer-  iASPP induces EMT and cisplatin resistance through miR-20a-FBXL5/BTG3 signaling in cervical cancer-  p53 gain of function mutations promote endometrial cancer progression and metastasis-  EZH2, MCL-1 and FOS gene are important oncogenes and EMT inducers in endometrial cancer- CRISPR/Cas9 and and genome editing-  ZEB1 acts as a novel EMT inducer in endometrial cancer-  BMI-1 gene functions as a important EMT inducer in endometrial cancer cells-  Musashi-2 (MSI-2) has a crucial role in promoting cervical cancer metastasis-  PD-L1 is a critical oncogenic factor in cervical cancer progression, and miR-140/142/340/383 regulate the expression of PD-L1 in cervical cancer-  Exploring lncRNA-Mediated Regulatory Networks in Endometrial Cancer-  Long noncoding RNA NEAT1 drives aggressive endometrial cancer progression via miR-361-regulated networks involving STAT3 and tumor microenvironment-related genes-  B7H3 As a Promoter of Metastasis and Promising Therapeutic Target-  miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway-  KLF4 expression enhances the efficacy of chemotherapy drugs in ovarian cancer cells-  Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells-  miR-34a, miR-424 and miR-513 inhibit MMSET expression to repress endometrial cancer cell invasion and sphere formation-  Molecular-targeted therapies and precision medicine for endometrial cancer-  Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelial to mesenchymal transition in ovarian cancer cells-  The Expression, Functions and Mechanisms of Circular RNAs in Gynecological Cancers-  Ovarian Primary and Metastatic Tumors Suppressed by Survivin Knockout or a Novel Survivin Inhibitor- url=https://hdl.handle.net/2115/61465-  LncRNA NEAT1-mediated miR-361 downregulation contributes to EMT of cervical cancer cells via increasing HSP90 expression: Epithelial-mesenchymal transition (EMT) is a key process contributing to cervical cancer (CC) metastasis, and microRNAs (miRNAs) modulate the expression of genes implicated in EMT. However, the accurate role of miR-361 in CC-associated EMT and the mechanisms underlying its function in CC remains largely unknown. The functional roles of miR-361 in CC cells were explored by a series of cell functional assays. Luciferase reporter assays were used to demonstrate the potential interaction between miR-361, HSP90, and long non-coding RNA (lncRNA) NEAT1. We detected a reduction of miR-361 expression in CC tissues compared with normal tissues, and miR-361 overexpression inhibited invasion and EMT phenotypes of CC cells by directly targeting a key EMT activator HSP90. Additionally, we detected significantly higher levels of HSP90 in CC tissues compared with normal tissues, and high expression of HSP90 predicted a poorer prognosis. We further identified NEAT1 as a significantly upregulated lncRNA in CC tissues and high expression of NEAT1 was associated with worse survival in CC patients. NEAT1 directly repressed miR-361 expression and played an oncogenic role in CC cell invasion and sphere formation. Conclusions: These results demonstrated that miR-361 directly targets HSP90 to inhibit the invasion and EMT features, and NEAT1 functions as an oncogenic lncRNA that suppresses miR-361 expression and induces EMT and sphere formation in CC cells, thus providing critical insights into the molecular pathways operating in this malignancy.-  MicroRNA-361: A Multifaceted Player Regulating Tumor Aggressiveness and Tumor Microenvironment Formation-  PD-L1 Is a Tumor Suppressor in Aggressive Endometrial Cancer Cells and Its Expression Is Regulated by miR-216a and lncRNA MEG3-  Background: Poorly differentiated endometrioid adenocarcinoma and serous adenocarcinoma represent an aggressive subtype of endometrial cancer (EC). Programmed death-ligand-1 (PD-L1) was known to exhibit a tumor cell-intrinsic function in mediating immune-independent tumor progression. However, the functional relevance of tumor cell-intrinsic PD-L1 expression in aggressive EC cells and the mechanisms regulating its expression remain unknown. Methods: PD-L1 expression in 65 EC tissues and 18 normal endometrium samples was analyzed using immunohistochemical staining. The effects of PD-L1 on aggressive EC cell growth, migration and invasion were investigated by cell functional assays. Luciferase reporter assays were used to reveal the microRNA-216a (miR-216a)-dependent mechanism modulating the expression of PD-L1. Results: Positive PD-L1 expression was identified in 84% of benign cases but only in 12% of the EC samples, and the staining levels of PD-L1 in EC tissues were significantly lower than those in the normal tissues. Higher PD-L1 expression predicts favorable survival in EC. Ectopic expression of PD-L1 in aggressive EC cells results in decreased cell proliferation and the loss of mesenchymal phenotypes. Mechanistically, PD-L1 exerts the anti-tumor effects by downregulating MCL-1 expression. We found that PD-L1 levels in aggressive EC cells are regulated by miR-216a, which directly targets PD-L1. We further identified a mechanism whereby the long non-coding RNA MEG3 represses the expression of miR-216a, thereby leading to increased PD-L1 expression and significant inhibition of cell migration and invasion. Conclusion: These results reveal an unappreciated tumor cell-intrinsic role for PD-L1 as a tumor suppressor in aggressive EC cells, and identify MEG3 and miR-216a as upstream regulators of PD-L1.

**Research Topics**
  microRNAs are novel prognostic biomarkers and EMT modulators, and act as either oncogeic miRNAs (OncomiRs) or tumor suppressors in endometrial cancer.-  Mutant p53 Gain-of-Function in Cancer: Besides the dominant negative effects upon wild type p53, increasing evidence suggests that p53 mutations acquire additional oncogenic functions, such as a gain-of-function (GOF), which actively drive cells toward invasion and metastasis7 through transactivation or transrepression of a large set of genes involved in regulation of cell adhesion, migration, and proliferation.-  Restoration of tumor suppressor miRNAs: The loss or down-regulation of a tumor suppressor miRNA could be overcome by the restoration of these silenced miRNAs.-  Blocking oncogenic miRNAs: Another strategy to target miRNA expression in cancer is to block the expression of an  oncogenic miRNA.-  CRISPR/Cas9-Mediated Genome Editing of Epigenetic Factors for Cancer Therapy.-  Interconnection between EMT and stemness in gynecological cancers.-  miRNAs regulates endometrial cancer metastasis through modulating tumor microenvironment.

**参考文献**
サムネイル
# eBook: Peixin Dong:  Molecular targets and targeted therapy. pp. 182-199. (Noriaki Sakuragi eds., Current Approaches to Endometrial Cancer. Future Medicine Ltd, UK), 2014.
# Peixin Dong*, Masanori Kaneuchi, Yosuke Konno, Hidemichi Watari, Satoko Sudo, Noriaki Sakuragi:  Emerging therapeutic biomarkers in endometrial cancer. Biomed Res Int 2013, 130362-130373, 2013 (*Corresponding author)
# Peixin Dong*, Yosuke Konno, Hidemichi Watari, Masayoshi Hosaka, Masayuki Noguchi, Noriaki Sakuragi:  The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer. J Transl Med 12, 231-240, 2014
# Peixin Dong*, Kei Ihira, Junichi Hamada, Hidemichi Watari, Takahiro Yamada, Masayoshi Hosaka, Sharon J.B. Hanle, Masataka Kudo and Noriaki Sakuragi:  Reactivating p53 functions by suppressing its novel inhibitor iASPP: a potential therapeutic opportunity in p53 wild-type tumors. Oncotarget 6, 19968-19975, 2015
# Dong P, Nabeshima K*, Nishimura N, Kawakami T, Hachisuga T, Kawarabayashi T, Iwasaki H:  Overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters in ovarian carcinomas. Cancer Lett 243, 120-127, 2006 (IF=4.960)
# Dong P, Tada M, Hamada J, Nakamura A, Moriuchi T, Sakuragi N*:  p53 dominant-negative mutation R273H promotes invasion and migration of human endometrial cancer HHUA cells. Clin Exp Metastasis 24, 471-483, 2007 (IF=3.770)
# Dong P*, Jia N, Xu ZJ, Liu YT, Li DJ, Feng YJ:  Silencing of IQGAP1 by shRNA inhibits the invasion of ovarian carcinoma HO-8910PM cells in vitro. J Exp Clin Cancer Res 27, 77-85, 2008 (IF=3.730)
# Jia N*, Dong P, Huang Q, Jin W, Zhang J, Dai Q, Liu S:  Cardioprotective effects of granulocyte colony-stimulating factor in Angiotensin-II Induced Cardiac Remodeling. Clin Exp Pharmacol Physiol 36, 262-266, 2009 (IF=2.370)
# Dong P*, Xu Z, Jia N, Li D, Feng Y:  Elevated expression of p53 gain-of-function mutation R175H in endometrial cancer cells can increase the invasive phenotypes by activation of the EGFR/PI3K/AKT pathway. Mol Cancer 8, 103-110, 2009 (IF=5.220)
# Peixin Dong, Masanori Kaneuchi, Hidemichi Watari, Junichi Hamada, Satoko Sudo, Jingfang Ju, Noriaki Sakuragi*:  miR-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer 10, 99-108, 2011 (IF=5.220)
# Nan Jia*, Peixin Dong, Ying Ye, Cheng Qian, Qiuyan Dai:  Allopurinol attenuates oxidative stress and cardiac fibrosis in angiotensin II-induced cardiac diastolic dysfunction. Cardiovasc Ther 30, 117-123, 2012 (IF=2.444)
# Tatsuya Kato, Hidemichi Watari*, Daisuke Endo, Takashi Mitamura, Tetsuji Odagiri, Yousuke Konno, Masayoshi Hosaka, Noriko Kobayashi, Yukiharu Todo, Satoko Sudo, Mahito Takeda, Peixin Dong, Masanori Kaneuchi, Masataka Kudo, Noriaki Sakuragi:  New revised FIGO 2008 staging system for endometrial cancer produces better discrimination in survival compared with the 1988 staging system. J Surg Oncol 106, 938-941, 2012 (IF=3.088)
# P Dong*, M Karaayvaz, N Jia, M Kaneuchi, J Hamada, H Watari, S Sudo, J Ju, N Sakuragi:  Mutant p53 gain-of-function induces epithelial–mesenchymal transition through modulation of the miR-130b–ZEB1 axis. Oncogene 32, 3286-3295, 2013 (IF=7.632)
# Haiyan Zhai, Mihriban Karaayvaz, Peixin Dong, Noriaki Sakuragi, Jingfang Ju*:  Prognostic significance of miR-194 in endometrial cancer. Biomark Res 1, 12-17, 2013 (IF=0.000)
# Peixin Dong*, Masanori Kaneuchi, Ying Xiong, Liping Cao, Muyan Cai, Xishi Liu, Sun-Wei Guo, Jingfang Ju, Nan Jia, Yosuke Konno, Hidemichi Watari, Masayoshi Hosaka, Satoko Sudo, Noriaki Sakuragi:  Identification of KLF17 as a novel epithelial to mesenchymal transition inducer via direct activation of TWIST1 in endometrioid endometrial cancer. Carcinogenesis 35, 760-768, 2014 (IF=5.698)
# Tetsuji Odagiri, Hidemichi Watari*, Tatsuya Kato, Takashi Mitamura, Masayoshi Hosaka, Satoko Sudo, Mahito Takeda, Noriko Kobayashi, Peixin Dong, Yukiharu Todo, Masataka Kudo, Noriaki Sakuragi:  Distribution of Lymph Node Metastasis Sites in Endometrial Cancer Undergoing Systematic Pelvic and Para-Aortic Lymphadenectomy: A Proposal of Optimal Lymphadenectomy for Future Clinical Trials. Ann Surg Oncol 21, 2755-2761, 2014 (IF=4.530)
# Peixin Dong*, Masanori Kaneuchi, Hidemichi Watari, Satoko Sudo, Noriaki Sakuragi:  miR-106b modulates epithelial-mesenchymal transition by targeting TWIST1 in invasive endometrial cancer cell lines. Molecular Carcinog 53, 349-359, 2014 (IF=4.180)
# Yosuke Konno, Peixin Dong*, Ying Xiong, Fumihiko Suzuki, Jiabin Lu, Muyan Cai, Hidemichi Watari, Takashi Mitamura, Masayoshi Hosaka, Sharon J B Hanley, Masataka Kudo, Noriaki Sakuragi:  MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells. Oncotarget 5, 6049-6062, 2014 (IF=6.402)
# Takashi Mitamura, Hidemichi Watari*, Lei Wang, Hiromi Kanno, Masaya Miyazaki, Makiko Kitagawa, Mohamed Kamel Hassan, Peixin Dong, Taichi Kimura, Mishie Tanino, Hiroshi Nishihara, Shinya Tanaka and Noriaki Sakuragi:  miR-31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway. Mol Cancer 13, 97-108, 2014 (IF=5.220)
# Hanley SJ*, Fujita H, Yokoyama S, Kunisawa S, Tamakoshi A, Dong P, Kobayashi N, Watari H, Kudo M, Sakuragi N:  HPV self-sampling in Japanese women: A feasibility study in a population with limited experience of tampon use. J Med Screen. 23, 164-70, 2016 (5-year IF =2.478)
# Dong P*, Ihira K, Xiong Y, Watari H, Hanley SJ, Yamada T, Hosaka M, Kudo M, Yue J, Sakuragi N:  Reactivation of epigenetically silenced miR-124 reverses the epithelial-to-mesenchymal transition and inhibits invasion in endometrial cancer cells via the direct repression of IQGAP1 expression. Oncotarget. 12, 20260-70, 2016 (5-year IF=5.312)
# Dong P*, Xiong Y, Watari H, Hanley SJ, Ihira K, Konno Y, Yamada T, Hosaka M, Kudo M, Yue J, Sakuragi N:  miR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells. Journal of Experimental & Clinical Cancer Research 35, 132-141, 2016 (5-year IF=4.590)
# Dong P*, Xiong Y, Watari H, Hanley SJ, Konno Y, Ihira K, Suzuki F, Yamada T, Kudo M, Yue J, Sakuragi N:  Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of miR-124. Sci Rep. 6, 35480-35491, 2016 (5-year IF=4.874)
# Huo W, Zhao G, Yin J, Xuan O, Wang Y, Yang C, Wang B, Dong P* (co-corresponding author), Wang Z, Watari H, Chaum E, Pfeffer L, Yue J:  Lentiviral CRISPR/Cas9 vector mediated miR-21 knockout inhibits the epithelial to mesenchymal transition in ovarian cancer cells. Journal of Cancer, 8, 57-64, 2017 (5-year IF=3.087)
# Wang B, Shen A, Ouyang X, Zhao G, Du Z, Huo W, Zhang T, Wang Y, Yang C, Dong P* (co-corresponding author), Watari H, Pfeffer LM, Yue J:  KLF4 expression enhances the efficacy of chemotherapy drugs in ovarian cancer cells. Biochem Biophys Res Commun. 484, 486-492, 2017 (5-year IF=2.354)
# Ihira K, Dong P* (co-first author), Xiong Y, Watari H, Konno Y, Hanley SJ, Noguchi M, Hirata N, Suizu F, Yamada T, Kudo M, Sakuragi N:  EZH2 inhibition suppresses endometrial cancer progression via miR-361/Twist axis. Oncotarget. 8, 13509-13520, 2017 (5-year IF=5.312)
# Xiong Y, Sun F, Dong P* (co-corresponding author), Watari H, Yue J, Yu M, Lan C, Wang Y, Ma Z:  iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling. Journal of Experimental & Clinical Cancer Research 36, 48-58, 2017 (5-year IF=4.590)
# Zhang Q, Dong P* (co-first author), Liu X, Sakuragi N, Guo SW.  Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis. Sci Rep. 7, 6804-6816, 2017 (5-year IF=4.874)
#  Zhao G, Wang Q, Gu Q, Dong P* (co-corresponding author), Watari H, Li W, Yue J. Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelial to mesenchymal transition in ovarian cancer cells. Oncotarget, accepted, 2017 (5-year IF=5.312)
#  Dong P*, Xiong Y, Hanley SJ, Yue J, Watari H. Musashi-2, a novel oncoprotein promoting cervical cancer cell growth and invasion, is negatively regulated by p53-induced miR-143 and miR-107 activation. Journal of Experimental & Clinical Cancer Research, accepted, 2017 (5-year IF=4.590)
#  Dong P*, Yue J. Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells. ONCOLOGY LETTERS, accepted, 2018

**外部リンク**
  董 培新-  Dong Peixin