Development of novel diagnosis and therapy against human oncogene hWAPL

针对人类癌基因 hWAPL 的新型诊断和治疗方法的开发

• 批准号: 20390116
• 负责人: KURODA Masahiko
• 金额: $ 10.07万
• 依托单位: Tokyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390116/
• 关键词: hWAPL; 子宮頚癌; miRNA; 分子標的治療; 細胞診; siRNA

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.

人WAPL（humanWAPL）基因是果蝇类Wapl基因的同源基因，编码调节异染色质结构的蛋白质。我们前期的研究表明，新基因hWAPL在宫颈不典型增生和宫颈癌中呈非计划性高水平表达。此外，NIH3T3细胞过度表达hWAPL发展成肿瘤后，注射到裸鼠，表明hWAPL在宫颈癌的发生和肿瘤进展中起着重要的作用，作为癌基因。由于使用小干扰RNA（siRNA）通过RNA干扰（RNAi）抑制hWAPL降低肿瘤生长，因此假定其成为分子靶向治疗的靶点的可能性。本研究鉴定了调控hWAPL基因表达的microRNA。这些microRNA与hWAPL基因的3'UTR结合，并参与hWAPL mRNA和蛋白的抑制。我们进一步推进分析，并将在未来研究microRNA治疗宫颈癌的有用性。

项目成果

Anthocyanidins-enriched bilberry extracts inhibit 3T3-L1 adipocyte differentiation via the insulin pathway.

• DOI: 10.1186/1743-7075-8-14
• 发表时间: 2011-03-08
• 期刊: Nutrition & metabolism
• 影响因子: 4.5
• 作者: Suzuki R;Tanaka M;Takanashi M;Hussain A;Yuan B;Toyoda H;Kuroda M
• 通讯作者: Kuroda M

HP1γ epigenetically regulates cell differentiation and exhibits potential as a therapeutic target for various types of cancers.

HP1γ 表观遗传调节细胞分化，并具有作为各种癌症治疗靶点的潜力。

• 发表时间: 2008
• 作者: Takanashi M;Oikawa K;Fujita K;Gotoh N;Kuroda M.
• 通讯作者: Kuroda M.

Therapeutic silencing of an endogenous gene by the siRNA cream in an arthritis model mouse.

siRNA 霜对关节炎模型小鼠的内源基因进行治疗性沉默。

• 发表时间: 2009
• 期刊: Gene Therapy 16
• 作者: Watanabe;Y.;Takahashi;T.;Ishii;N.;Ito;M.;Minegishi;M.;Tsuchiya;S.;Sugamura;K;Xu M;Takanashi M
• 通讯作者: Takanashi M

Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development

• DOI: 10.1111/j.1440-1827.2010.02526.x
• 发表时间: 2010-05-01
• 期刊: PATHOLOGY INTERNATIONAL
• 影响因子: 2.2
• 作者: Shigoka, Masatoshi;Tsuchida, Akihiko;Kuroda, Masahiko
• 通讯作者: Kuroda, Masahiko

がん転移研究の実験手法 転移研究を目的とした組織アレイの作製法

癌症转移研究的实验方法 用于转移研究的组织阵列的制备方法

• 发表时间: 2008
• 作者: 済木育夫;愛甲 孝
• 通讯作者: 愛甲 孝