Open AccessMicroRNA‐143/Musashi‐2/ KRAS cascade contributes positively to carcinogenesis in human bladder cancer
Author(s) -
Tsujino Takuya,
Sugito Nobuhiko,
Taniguchi Kohei,
Honda Ryo,
Komura Kazumasa,
Yoshikawa Yuki,
Takai Tomoaki,
Minami Koichiro,
Kuranaga Yuki,
Shinohara Haruka,
Tokumaru Yoshihisa,
Heishima Kazuki,
Inamoto Teruo,
Azuma Haruhito,
Akao Yukihiro
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14035
Subject(s) - kras , carcinogenesis , microrna , cancer research , messenger rna , biology , rna , rna binding protein , translation (biology) , cancer , microbiology and biotechnology , gene , mutation , genetics
It has been well established that micro RNA (miR)‐143 is downregulated in human bladder cancer ( BC ). Recent precision medicine has shown that mutations in BC are frequently observed in FGFR 3, RAS and PIK 3 CA genes, all of which correlate with RAS signaling networks. We have previously shown that miR‐143 suppresses cell growth by inhibiting RAS signaling networks in several cancers including BC . In the present study, we showed that synthetic miR‐143 negatively regulated the RNA ‐binding protein Musashi‐2 ( MSI 2) in BC cell lines. MSI 2 is an RNA ‐binding protein that regulates the stability of certain mRNA s and their translation by binding to the target sequences of the mRNA s. Of note, the present study clarified that MSI 2 positively regulated KRAS expression through directly binding to the target sequence of KRAS mRNA and promoting its translation, thus contributing to the maintenance of KRAS expression. Thus, miR‐143 silenced KRAS and MSI 2, which further downregulated KRAS expression through perturbation of the MSI 2/ KRAS cascade.