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Project

[Functional analyses of oncogenic microRNA by genome editing and development of innovative genome-based drug discovery for bladder cancer.]

Original in Japanese: Functional analyses of oncogenic microRNA by genome editing and development of innovative genome-based drug discovery for bladder cancer.

Funder: Japan Society for the Promotion of Science

Funding period
JPY 17.0 M
USD 155 K
Funding amount
Abstract
[By next-generation sequencermiRNAExpression analysis was performed and expression was significantly reduced in bladder cancer 60個のmiRNAI have analyzed from the top of the list. As a result, in bladder cancer clinical specimens,miR-223Expression was significantly lower in bladder cancer tissues than in normal tissues. In functional analysis,miR-223Inhibits proliferation, migration and invasion of bladder cancer cell lines, and induced apoptosis.in silico解析にてmiR-223のputative target geneとしてWDR62を選出し、luciferase reporter assayによってmiR-223It was confirmed to be directly controlled by.si-WDR62In the functional analysis usingWDR62のknockdown, The proliferation, migration, and invasion ability of the bladder cancer cell line was suppressed, and apoptosis was induced.TCGAデーIn the analysis using the database,miR-223の低発現とLymphovascular invasionやDistant metastasisとの関係や、WDR62の高発現とPathological subtype、Tumor grade、Distant metastasis、StageHas been suggested to be related to. furtherthe cancer genome atlas (TCGA) In the bladder cancer cohort ofHRASExpression in cancer samples is significantly higher than in normal samples,HRASThe expression was significantly higher in the bladder cancer specimens with the mutations of.Salirasibおよびsi-HRAS transductionHRASIt inhibited cell proliferation, migration and invasion ability in bladder cancer cells with and without mutations. In proteome analysis,salirasibIn the treated group, metabolic pathways such as oxidative phosphorylation were significantly suppressed.]
Original in Japanese
次世代シークエンサーによるmiRNA発現解析を行い、膀胱癌で有意に発現が低下していた60個のmiRNAの中でリストの上位のものから解析を行ってきた。その結果、膀胱癌臨床検体において、miR-223の発現が正常組織より膀胱癌組織で有意に低下していた。機能解析では、miR-223によって膀胱癌細胞株の増殖・遊走・浸潤能が抑制され、アポトーシスが誘導された。in silico解析にてmiR-223のputative target geneとしてWDR62を選出し、luciferase reporter assayによってmiR-223によって直接的に制御されていることを確認した。si-WDR62を用いた機能解析では、WDR62のknockdownが膀胱癌細胞株の増殖・遊走・浸潤能が抑制され、アポトーシスが誘導された。TCGAデータベースを用いた解析では、miR-223の低発現とLymphovascular invasionやDistant metastasisとの関係や、WDR62の高発現とPathological subtype、Tumor grade、Distant metastasis、Stageとの関係が示唆された。さらにthe cancer genome atlas (TCGA) の膀胱癌コホートでは、HRASの発現が癌検体では正常検体と比べて有意に高く、 HRASの突然変異を有する膀胱癌検体では突然変異のない膀胱癌検体と比べてその発現が有意に高かった。Salirasibおよびsi-HRASの形質導入は、HRAS突然変異の有無にかかわらず、膀胱癌細胞において細胞増殖、遊走および浸潤能を阻害した。プロテオーム解析では、salirasib処理した群において、酸化的リン酸化反応などの代謝経路が有意に抑制されていた。
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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Biotechnology

  • RCDC

    Human Genome

  • RCDC

    Cancer

  • RCDC

    Genetics

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science