Development of novel diagnosis and therapy against human oncogene hWAPL

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390116
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical University
• Principal Investigator: KURODA Masahiko Tokyo Medical University, 医学部, 主任教授 (80251304)
• Project Period (FY): 2008 – 2010
• Keywords: hWAPL / 子宮頚癌 / miRNA / 分子標的治療

Research Abstract

Human WAPL (hWAPL) gene is human homologue of wings apart-like (wapl) gene which encodes a protein that regulates heterochromatin structure of Drosophilia. Our previous study demonstrated that the novel human gene hWAPL showed the unscheduled high level expression in cervical dysplasia and carcinoma. In addition, NIH3T3 cells overexpressing hWAPL developed into tumours upon injection into nude mice, suggesting that hWAPL plays a significant role in cervical carcinogenesis and tumour progression as an oncogene. Because the repression of hWAPL by RNA interference (RNAi) using small interfering RNA (siRNA) decrease the tumor growth, the possibility that it becomes the target of the molecular target therapy is assumed. We identified the microRNA which regulated the expression of hWAPL gene this time. These microRNAs bound to 3'UTR of hWAPL gene and were shown to participate in repression of hWAPL mRNA and protein. We push forward analysis more and will investigate usefulness of the treatment of uterine cervical cancer with microRNA in future.

Research Products

• [Journal Article] Anthocyanidins-enriched bilberry extracts inhibit 3T3-L1 adipocyte differentiation via the insulin pathway. (2011)
  • Author(s): Suzuki R, Tanaka M, Takanashi M, Hussain A, Yuan B, Toyoda H, Kuroda M
  • Journal Title: Nutr Metab (Lond). 8 Pages: 14
  • Peer Reviewed
• [Journal Article] The progression of liver fibrosis is related with overexpression of the miR-199 and 200 families. (2011)
  • Author(s): Murakami Y, Toyoda H, Tanaka M, Kuroda M, Harada Y, Matsuda F, Tajima A, Kosaka N, Ochiya T, Shimotohno K
  • Journal Title: PLoS One. 6(1) Pages: e16081
  • Peer Reviewed
• [Journal Article] Clinical Impact of Down-regulated Plasma miR-92a Levels in Non-Hodgkin's Lymphoma. (2011)
  • Author(s): Ohyashiki K, Umezu T, Yoshizawa S, Ito Y, Ohyashiki M, Kawashima H, Tanaka M, Kuroda M, Ohyashiki JH
  • Journal Title: PLoS ONE. 6(2) Pages: e16408
  • Peer Reviewed
• [Journal Article] Impact on cell to plasma ratio of miR-92a in patients with acute leukemia : in vivo assessment of cell to plasma ratio of miR-92a. (2010)
  • Author(s): Ohyashiki JH, Umezu T, Kobayashi C, Hamamura RS, Tanaka M, Kuroda M, Ohyashiki K
  • Journal Title: BMC Res Notes. 3 Pages: 347
  • Peer Reviewed
• [Journal Article] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development. (2010)
  • Author(s): Shigoka M, Tsuchida A, Matsudo T, Nagakawa Y, Saito H, Suzuki Y, Aoki T, Murakami Y, Toyoda H, Kumada T, Bartenschlager R, Kato N, Ikeda M, Takashina T, Tanaka M, Suzuki R, Oikawa K, Takanashi M, Kuroda M
  • Journal Title: Pathol Int. 60(5) Pages: 351-357
  • Peer Reviewed
• [Journal Article] Suppression of Experimental Autoimmune Uveoretinitis by Inducing Differention of Regulatory T Cells via Activation of Aryl Hydrocarbon Receptor. (2010)
  • Author(s): Zhang L, Ma J, Takeuchi M, Usui Y, Hattori T, Okunuki Y, Yamakawa N, Kezuka T, Kuroda M, Goto H
  • Journal Title: Investigative Ophthalmology & Visual Science. 51(4) Pages: 2109-2117
  • Peer Reviewed
• [Journal Article] FRS2beta, a potential prognostic gene for non-small cell lung cancer, encodes a feedback inhibitor of EGF receptor family members by ERK binding. (2010)
  • Author(s): Iejima D, Minegishi Y, Takenaka K, Siswanto A, Watanabe M, Huang L, Watanabe T, Tanaka F, Kuroda M, Gotoh N
  • Journal Title: Oncogene. 29(21) Pages: 3087-3099
  • Peer Reviewed
• [Journal Article] Cytoprotective Effect of Imatinib Mesylate in Non-BCR-ABL-expressing Cells and Autophagosome Formation. (2010)
  • Author(s): Ohtomo T, Miyazawa K, Naito M, Moriya S, Kuroda M, Itoh M, Tomoda A
  • Journal Title: BBRC. 391(1) Pages: 310-315
  • Peer Reviewed
• [Journal Article] Gene set enrichment analysis provides insight into novel signaling pathways in breast cancer stem cells. (2010)
  • Author(s): Murohashi M, Hinohara K, Kuroda M, Isagawa T, Tsuji S, Kobayashi S, Umezawa K, Tojo A, Aburatani Hand Gotoh N
  • Journal Title: British journal of cancer. 102(1) Pages: 206-212
  • Peer Reviewed
• [Journal Article] MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. (2009)
  • Author(s): Yamamoto Y, Kosaka N, Tanaka M, Koizumi F, Kanai Y, Mizutani T, Murakami Y, Kuroda M, Miyajima A, Kato T, Ochiya T
  • Journal Title: Biomarkers. 14(7) Pages: 529-538
  • Peer Reviewed
• [Journal Article] Mucinous Carcinoma of the Rectosigmoid Colon, Transforming from a Pedunculated (Ip type) Polypoid Cancer in about One Year, Report of a Case. (2009)
  • Author(s): Higuchi R, Nakamura F, Matsuura Y, Hattori K, Suda H, Kawazaki H, Ohta A, Kuroda M, Matsubayashi J
  • Journal Title: Stomach and Intestine (Tokyo). 44(11) Pages: 1777-1784
  • Peer Reviewed
• [Journal Article] USP15 plays an essential role for caspase-3 activation during Paclitaxel-induced apoptosis. (2009)
  • Author(s): Xu M, Takanashi M, Oikawa K, Tanaka M, Nishi H, Isaka K, Kudo M, Kuroda M
  • Journal Title: Biochem Biophys Res Commun. 388(2) Pages: 366-371
  • Peer Reviewed
• [Journal Article] Therapeutic silencing of an endogenous gene by the siRNA cream in an arthritis model mouse. (2009)
  • Author(s): Takanashi M, Oikawa K, Sudo K, Tanaka M, Fujita K, Kasper R, Matsuzaki M, Kuoda M
  • Journal Title: Gene Therapy. 16(8) Pages: 982-989
  • Peer Reviewed
• [Journal Article] Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. (2009)
  • Author(s): Tanaka M, Oikawa K, Takanashi M, Kudo M, Ohyashiki J, Ohyashiki K, Kuroda M
  • Journal Title: PloS ONE 4(5) Pages: e5532
  • Peer Reviewed
• [Journal Article] HPly epigenetically regulates cell differentiation and exhibits potential as a therapeutic target for various types of cancers. (2009)
  • Author(s): Takanashi M, Oikawa K, Fujita K, Kudo M, Kinoshita M, Kuroda M
  • Journal Title: Am J Pathol. 174(1) Pages: 309-316
  • Peer Reviewed
• [Journal Article] Expression of G-protein-coupled receptor kinase 4 is associated with breast cancer tumorigenesis. (2008)
  • Author(s): Matsubayashi J, Takanashi M, Oikawa K, Mingli Xu, Mukai K, Kuroda M, Mukai K
  • Journal Title: J Pathol. 216 Pages: 317-327
  • Peer Reviewed
• [Journal Article] Expression of various types of alternatively spliced WAPL transcripts in human cervical epithelia. (2008)
  • Author(s): Oikawa K, Akiyoshi A, Tanaka M, Takanashi M, Nishi H, Isaka K, Kiseki H, Idei T, Tsukahara Y, Hashimura N, Mukai K, Kuroda M
  • Journal Title: Gene. 423(1) Pages: 57-62
  • Peer Reviewed
• [Journal Article] Dioxin interferes in chromosomal positioning through the aryl hydrocarbon receptor. (2008)
  • Author(s): Oikawa K, Yoshida K, Takanashi M, Tanabe H, Kiyuna T, Ogura M, Saito A, Umezawa A, Kuroda M
  • Journal Title: Biochem Biophys Res Commun. 374(2) Pages: 361-364
  • Peer Reviewed
• [Presentation] Deregulation of miR-92a expression is implicated in colon cancer development. (2010)
  • Author(s): Ohno S, Tanaka M, Suzuki R, Naraso, Go I, Fujita K, Takanashi M, Kuroda M.
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] エキソソーム内のマイクロRNAによる細胞間情報伝達効率 (2010)
  • Author(s): 田中正視、上田しのぶ、大野慎一郎、高梨正勝、柴田篤志、黒田雅彦
  • Organizer: 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] 大腸癌におけるmiR-17-92クラスターの解析 (2010)
  • Author(s): 那日蘇、呉偉紅、藤田浩司、松山永久、田中正視、鈴木理英子、高梨正勝、大野慎一郎、倉田厚、黒田雅彦
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-20100924
• [Presentation] miR-92aの発現は大腸癌の増殖に関与する (2010)
  • Author(s): 大野慎一郎、田中正視、鈴木理英子、那日蘇、呉偉紅、藤田浩司、高梨正勝、黒田雅彦
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-20100924
• [Presentation] microRNAプロファィルとC型慢性肝炎へのインターフェロン治療効果 (2010)
  • Author(s): 田中正視、村上善基、下遠野邦忠、田嶋敦、高梨正勝、大野慎一郎、鈴木理英子、黒田雅彦
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-20100924
• [Presentation] EGFR遺伝子を標的とするmiRNAの単離と解析 (2010)
  • Author(s): 山口学、大平達夫、黒田雅彦、田中正視、高梨正勝、大野慎一郎、片場寛明、吉田浩一、垣花昌俊、臼田実男、梶原直央、内田修、池田徳彦
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-20100924
• [Presentation] 骨髄間葉系幹細胞による皮膚炎モデルマウスへの症状の抑制効果について (2010)
  • Author(s): 高梨正勝、須藤カツ子、石川章夫、黒田雅彦
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20100427-20100429
• [Presentation] LNA probeを用いたin situ hybridizationによるmiRNAの検出 (2010)
  • Author(s): 藤田浩司、田中正視、高梨正勝、黒田雅彦
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20100427-20100429
• [Presentation] Potential roles of NF kaooa B pathways in breast cancer-initiating cells. (2010)
  • Author(s): Hinohara K, Murohashi M, Kuroda M., Isagawa T, Tsuji S, Kobayashi S, Umezawa K, Tojo A, Aburatani H, Goto N
  • Organizer: AACR, 101^<st> Annual Meeting
  • Place of Presentation: Washington, DC USA
  • Year and Date: 20100417-20100421
• [Presentation] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development. (2010)
  • Author(s): Tanaka M, Tsuchida A, Shigoka M, Aoki T, Takashina T, Takanashi M, Murakami Y, Kuroda M.
  • Organizer: AACR, 101^<st> Annual Meeting
  • Place of Presentation: Washington, DC USA
  • Year and Date: 20100417-20100421
• [Presentation] Potential roles of NF-kB pathways in breast cancer-initiating cells. (2009)
  • Author(s): Hinohara K, Murohashi M, Kuroda M, Isagawa T, Tsuji S, Kobayashi S, Umehara K, Tojo A, Aburatani H, Gotoh N
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] Circulating microRNAs in plasma as novel biomarkers. (2009)
  • Author(s): Tanaka M, Suzuki R, Murakami Y, Toyoda H,Matsudo T, Shigoka M, Tsutida A, Aoki T, Ohyashiki J, Ohyashiki K, Kuroda M.
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] The chimeric oncoprotein TLS-CHOP represses the expression of an anticancer molecule through induction of specific microRNAs. (2009)
  • Author(s): Oikawa K, Tanaka M, Ito S, Takanashi M, Uetani K, Muragaki Y, Kuroda M.
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] Therapic silencing of an endogenous gene by siRNA cream in an arthritis model mouse. (2009)
  • Author(s): Takanashi M, Oikawa K, Sudo K, Tanaka M, Nakae S, Kuroda M.
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] Bilberry extract inhibits adipocyte diffentiation. (2009)
  • Author(s): Suzuki R, Tanaka M, Toyoda H, Kuroda M.
  • Organizer: 第32回日本分子生物学会年会(MBSJ2009)
  • Place of Presentation: 横浜
  • Year and Date: 20091209-20091212
• [Presentation] Down-regulation of miR-in human plasma is a novel marker for acure leukemia patients. (2009)
  • Author(s): Talcnaka M, Oikawa K, Ohyashiki K, Ohyashiki J, Kuroda M.
  • Organizer: 68^<th> Annual Meeting ofthe Japanese Cancer Association.
  • Place of Presentation: 横浜
  • Year and Date: 20091001-20091003
• [Presentation] Molecular signatures of tumor-intiating cells in human breast cancer cell lines. (2009)
  • Author(s): Murohashi M, Hinohara K, Kuroda M, Isagawa T, Tsuji S, Aburatani H, Gotoh N
  • Organizer: 68^<th> Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: 横浜
  • Year and Date: 20091001-20091003
• [Presentation] Oncofetal microRNA as a potential diagnostic marker for hepatocellularcarcinoma. (2009)
  • Author(s): Kosaka N, Yamamoto Y, Murakami Y, Kuroda M, Ochiya T
  • Organizer: 68^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 横浜
  • Year and Date: 20091001-20091003
• [Presentation] Autophagy Inducing Effect of Imatinib Mesylate in Non-BCR-ABL Expressing Cells along with Suppression of ER Stress. (2009)
  • Author(s): Ohtomo T, Miyazawa K, Kuroda M, Tomoda A
  • Organizer: 68^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: 横浜
  • Year and Date: 20091001-20091003
• [Presentation] miRNAによる癌診断の臨床応用 (2009)
  • Author(s): 黒田雅彦
  • Organizer: 第1回日本RNAi研究会
  • Place of Presentation: 広島
  • Year and Date: 20090828-20090829
• [Presentation] ヒト血漿におけるmiR-92の下方制御は急性白血病の新規マーカーである (2009)
  • Author(s): 田中正視、及川恒輔、大屋敷一馬、大屋敷純子、黒田雅彦
  • Organizer: 日本癌学会総会記事(0546-0476)68回Page145
  • Year and Date: 20090800
• [Presentation] Effects of Dioxin on Vascular Endothelial Growth Factor(VEGF) Production in the Retina Associated with Chroidal Neavascularization. (2009)
  • Author(s): Takeuchi A, Takeuchi M, Oikawa K, Sonoda K, Usui Y, Okunuki Y, Takeda A, Oshima Y, Yoshida K, Usui M, Goto H, Kuroda M.
  • Organizer: Invest Ophthalmol Vis Sci.(50(7) : 3410-6)
  • Year and Date: 20090700
• [Presentation] A functional genomic screen identifies a role of USP15 and Septin 10 in spindle-checkpoint and Paclitaxel-resistance in human cancers. (2009)
  • Author(s): Xu M, Takanashi M, Oikawa K, Tanaka M, Nishi H, Isaka K, Kudo M, Kuroda M.
  • Organizer: AACR, 100^<th> Annual Meeting
  • Place of Presentation: Denver, Colorado USA
  • Year and Date: 20090418-20090422
• [Presentation] Therapeutic Silencing of an Endogenous Gene by the siRNA Cream in an Arthritis model Mouse. (2009)
  • Author(s): 黒田雅彦
  • Organizer: KEYSTONE SYMPOSIA on Molecular and Cellular Biology, Therapeutic Modulation of RNA Using Oligonucleotides
  • Place of Presentation: Canada
  • Year and Date: 20090208-20090213
• [Presentation] 乳癌におけるG protein-coupled Receptor Kinase 4の役割とその関連分子の同定 (2009)
  • Author(s): 黒田雅彦、高梨正勝、工藤玄恵、松林純、長尾俊孝、斉藤彰、田伏洋、木下雅雄
  • Organizer: 第5回日本臨床プロテオーム研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-05-09
• [Presentation] 脂肪細胞分化に関与するmicroRNAの探索 (2008)
  • Author(s): 鈴木理英子、及川恒輔、田中正視、高梨正勝、黒田雅彦
  • Organizer: 第31回日本分子生物学会年会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 20081209-20081212
• [Presentation] ヒト子宮頸部病変におけるWAPL遺伝子の多様な選択的スプライシングバリアントの発現 (2008)
  • Author(s): 及川恒輔、秋好歩美、田中正視、高梨正勝、黒田雅彦
  • Organizer: 第31回日本分子生物学会年会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 20081209-20081212
• [Presentation] Expression of various types of alternatively spliced WAPL transcripts in human cervical epithelia. (2008)
  • Author(s): Oikawa K, Takanashi M, Kuroda M
  • Organizer: 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 20081028-20081030
• [Presentation] Analysis of tumor initiating cells/cancer stem cells in human breast cancer cell lines. (2008)
  • Author(s): Murohashi M, Kuroda M, Kobayashi S, Tojo A, Gotoh N
  • Organizer: 67^<th> Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 20081028-20081030
• [Presentation] HP1γ epigenetically regulates cell differentiation and exhibits potential as a therapeutic target for various types of cancers. (2008)
  • Author(s): Takanashi M, Oikawa K, Fujita K, Gotoh N, Kuroda M.
  • Organizer: AACR-NCI-EORTC Symposium Molecular Targets and Cancer Therapeutics
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 20081021-20081024
• [Presentation] 軟部腫瘍の病理診断における免疫組織化学の新展開 (2008)
  • Author(s): 黒田雅彦、及川恒輔、服部宏行、山本謙吾、向井清
  • Organizer: 第41回日本整形外科学会 骨・軟部腫瘍学術集会
  • Place of Presentation: 浜松
  • Year and Date: 20080717-20080718
• [Presentation] 粘液型脂肪肉腫とPRG4の各スプライシングバリアントとの関わり (2008)
  • Author(s): 鈴木理英子、及川恒輔、高梨正勝、黒田雅彦、向井清
  • Organizer: 第97回日本病理学会
  • Place of Presentation: 石川県
  • Year and Date: 20080515-20080517
• [Presentation] 粘液型及び円形細胞型脂肪肉腫におけるTLS-CHOPキメラ癌タンパク質の癌細胞増殖制御機構 (2008)
  • Author(s): 及川恒輔、高梨正勝、黒田雅彦、向井清
  • Organizer: 第97回日本病理学会
  • Place of Presentation: 石川県
  • Year and Date: 20080515-20080517
• [Presentation] 研究費申請書の書き方のポイント (2008)
  • Author(s): 向井清、黒田雅彦
  • Organizer: 第97回日本病理学会
  • Place of Presentation: 石川県(特別発言)
  • Year and Date: 20080515-20080517
• [Presentation] FRS2beta adaptor is a novel tumor suppressor for breast cancer by attenuating ErbB signaling. (2008)
  • Author(s): Watanabe T, Kuroda M, Gotoh N
  • Organizer: AACR, Annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20080412-20080416
• [Presentation] Ip型ポリープから発育伸展した直腸粘液癌の1例 (2008)
  • Author(s): 樋口良太、可児希、橋本剛、戸田隆洋、中村文彦、松浦良徳、服部克哉、須田浩晃、太田昭彦、剛崎寛徳、黒田雅彦
  • Organizer: 早期胃癌研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-18
• [Remarks] ホームページ等
  • URL: http://www.tokyo-med.ac.ip/molpathol/
• [Patent(Industrial Property Rights)] 新規な癌遺伝子、該癌遺伝子由来の組換えタンパク質、およびそれらの用途 (2011)
  • Inventor(s): 黒田雅彦、齋藤彰
  • Industrial Property Rights Holder: 東京医科大学、日本電気(株)
  • Industrial Property Number: 特許権US出願(分割2),7893246
  • Acquisition Date: 2011-02-22
• [Patent(Industrial Property Rights)] 新規な癌遺伝子、該癌遺伝子由来の組換えタンパク質、およびそれらの用途 (2010)
  • Inventor(s): 黒田雅彦、齋藤彰
  • Industrial Property Rights Holder: 東京医科大学、日本電気(株)
  • Industrial Property Number: 特許権中国出願(分割),200610149330.2
  • Acquisition Date: 2010-06-09
• [Patent(Industrial Property Rights)] 新規な癌遺伝子、該癌遺伝子由来の組換えタンパク質、およびそれらの用途 (2008)
  • Inventor(s): 黒田雅彦、齋藤彰
  • Industrial Property Rights Holder: 東京医科大学、日本電気(株)
  • Industrial Property Number: 特許権US出願(分割1),7432358
  • Acquisition Date: 2008-10-07
• [Patent(Industrial Property Rights)] 新規な癌遺伝子、該癌遺伝子由来の組換えタンパク質、およびそれらの用途 (2008)
  • Inventor(s): 黒田雅彦、齋藤彰
  • Industrial Property Rights Holder: 東京医科大学、日本電気(株)
  • Industrial Property Number: 特許権US出願,7358350
  • Acquisition Date: 2008-07-15