Role of miR-143 and -145 in carcinogenesis of colon cancer

miR-143和-145在结肠癌发生中的作用

• 批准号: 20590419
• 负责人: AKAO Yukihiro
• 金额: $ 3.08万
• 依托单位: Gifu International Institute of Biotechnology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-20590419/
• 关键词: マイクロRNA; がん; 大腸腫瘍; microRNA-143、-145; c-myc; 消化管腫瘍; 癌; 翻訳制御; がん抑制遺伝子; ヌクレアーゼ耐性; 化学修飾; 増殖抑制; 腫瘍縮小効果; がん抑制マイクロRNA; ERK5

We examined the expression levels of miRNAs (miRs) in colorectal tumors (63 cancer specimens and 65 adenoma specimens) and paired non-tumorous tissues. Decreased expression of miR-143 and -145 was frequently observed in the adenomas and cancers tested, compared with miR-34a down-regulation and miR-21 up-regulation. Expression profiles of miR-143 and -145 were not associated with any clinical features. Since the down-regulation of miR-143 and -145 was observed even in the early phase of adenoma formation, the decreased expression of both miRs would appear to contribute mainly to the initiation step of tumorigenesis, not to the progression stage, and not to clinical prognostic factors. For clinical application, we changed the sequences of the passenger strand in the miR-143 duplex and performed chemical modification at the 3'-overhang portion of miR-143, leading to greater activity and stability to nuclease. The cell growth inhibitory effect of the chemically modified synthetic miR-143 in vitro was greater than that of endogenous miR-143. The miR-143 showed a significant tumor-suppressive effect on xenografted tumors of DLD-1 human colorectal cancer cells.

我们检测了miRNAs(MiRs)在结直肠癌(63例癌组织和65例腺瘤组织)和配对的非肿瘤组织中的表达水平。与miR-34a下调和miR-21上调相比，miR-143和-145在腺瘤和癌中的表达经常降低。MiR-143和-145的表达谱与任何临床特征无关。由于miR-143和miR-145的表达下调甚至在腺瘤形成的早期就观察到了，所以这两种miR的表达降低似乎主要是在肿瘤发生的起始阶段，而不是在进展期，也不是临床预后因素。为了临床应用，我们改变了miR-143双链中的客体链的序列，并在miR-143的3‘-突出部分进行了化学修饰，从而对核酸酶进行了更高的活性和稳定性。化学修饰的合成miR-143体外对细胞生长的抑制作用强于内源性miR-143。MiR-143对DLD-1人结直肠癌细胞移植瘤有明显的抑瘤作用。

项目成果

B細胞腫瘍と microRNAs

B 细胞肿瘤和 microRNA

• 发表时间: 2008
• 期刊: 科学評論社 血液・腫瘍科 第56巻
• 作者: 赤尾幸博;中川義仁;直江知樹
• 通讯作者: 直江知樹

細胞を用いた新規なRNA医薬搬送システムの構築-患者の白血球に目的のRNA分子を導入し体内に戻す-岐阜大学大学院連合創薬

利用细胞构建新型RNA药物输送系统 - 将所需的RNA分子导入患者的白细胞并将其返回体内 - 岐阜大学研究生院药物发现联盟

• 发表时间: 2010
• 作者: 赤尾幸博;野口俊介;飯尾明夫;本間季里;辻和宏;赤尾幸博
• 通讯作者: 赤尾幸博

Transcriptional and post-translational regulation of miR-143/145 expression through host gene, NCR143/145 in cancers

癌症中通过宿主基因 NCR143/145 进行 miR-143/145 表达的转录和翻译后调控

• 发表时间: 2010
• 作者: 飯尾明夫;赤尾幸博
• 通讯作者: 赤尾幸博

MicroRNA-141 and-200a Are Involved in Bone Morphogenetic Protein-2-induced Mouse Pre-osteoblast Differentiation by Targeting Distal-less Homeobox 5

• DOI: 10.1074/jbc.m109.014001
• 发表时间: 2009-07-17
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Itoh, Tomohiro;Nozawa, Yoshinori;Akao, Yukihiro
• 通讯作者: Akao, Yukihiro

Decreased expression of microRNAs-143 and-145 in human gastric cancers.

人类胃癌中 microRNA-143 和-145 的表达降低。

• 发表时间: 2009
• 期刊: Oncology 77
• 作者: Takagi T;Iio A;Nakagawa Y;Naoe T;Tanigawa N;Akao Y.
• 通讯作者: Akao Y.