Anti-cancer Effects of a Chemically Modified miR-143 on Bladder Cancer by Either Systemic or Intravesical Treatment | Zendy

Yuki Yoshikawa | Zendy; Kohei Taniguchi | Zendy; Takuya Tsujino | Zendy; Kazuki Heishima | Zendy; Teruo Inamoto | Zendy; Tomoaki Takai | Zendy; Koichiro Minami | Zendy; Haruhito Azuma | Zendy; Kanjiro Miyata | Zendy; Kotaro Hayashi | Zendy; Kazunori Kataoka | Zendy; Yukihiro Akao | Zendy

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Anti-cancer Effects of a Chemically Modified miR-143 on Bladder Cancer by Either Systemic or Intravesical Treatment

Author(s) -

Yuki Yoshikawa,

Kohei Taniguchi,

Takuya Tsujino,

Kazuki Heishima,

Teruo Inamoto,

Tomoaki Takai,

Koichiro Minami,

Haruhito Azuma,

Kanjiro Miyata,

Kotaro Hayashi,

Kazunori Kataoka,

Yukihiro Akao

Publication year - 2019

Publication title -

molecular therapy — methods and clinical development

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.285

H-Index - 32

ISSN - 2329-0501

DOI - 10.1016/j.omtm.2019.02.005

Subject(s) - protein kinase b , bladder cancer , microrna , cancer research , ectopic expression , effector , in vivo , cancer , mapk/erk pathway , pathogenesis , guanosine , apoptosis , pi3k/akt/mtor pathway , chemistry , medicine , signal transduction , pharmacology , microbiology and biotechnology , biology , immunology , biochemistry , genetics , gene

We developed a novel chemically modified miR-143 (miR-143#12), and with it we investigated the contribution of miR-143 to the pathogenesis of bladder cancer (BC), in which miR-143 is extremely downregulated. Since miR-143 silenced K-RAS and RAS effector-signaling molecules Erk and Akt, we performed the ectopic expression of miR-143 in human BC 253J-BV cells, and we examined the growth inhibition and the mechanism of it in vitro and in orthotopic model mice. As a result, miR-143#12 induced a marked growth inhibition with apoptosis through impairing RAS-signaling networks, including SOS1, which exchanges guanosine diphosphate (GDP)/RAS for active guanosine triphosphate (GTP)/RAS. In the in vivo study, miR-143#12 exhibited a marked anti-tumor activity by either systemic or intravesical administration with polyionic copolymer (PIC) as the carrier, compared with the activity obtained by use of lipofection. These findings raised the possibility that the chemically modified miR-143#12 would be a candidate of microRNA (miRNA) medicine for BC delivered by intravesical infusion.

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