MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells

Koichiro Minami, Kohei Taniguchi, Nobuhiko Sugito, Yuki Kuranaga, Teruo Inamoto, Kiyoshi Takahara, Tomoaki Takai, Yuki Yoshikawa, Satoshi Kiyama, Yukihiro Akao, Haruhito Azuma

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The Warburg effect is a well-known feature in cancer-specific metabolism. We previously reported on the role of microRNA (miR)-145 as a tumor-suppressor in human bladder cancer (BC) cells. In this study, we reveal that miR-145 decreases the Warburg effect by silencing KLF4 in BC cells. The expression levels of miR-145 were significantly lower in clinical BC samples and BC cell lines compared to those in normal tissues and HUC cells. Luciferase assay results showed that miR-145 directly bound to 3'UTR of KLF4, which was shown to be overexpressed in the clinical BC samples using Western blot analysis and immunohistochemistry. Remarkable growth inhibition and apoptosis were induced by the ectopic expression of miR-145 or by the gene silencing of KLF4 (siR-KLF4). Also, Warburg effect-related genes such as PTBP1/PKMs were regulated by the transfection of BC cells with miR-145 or siR-KLF4. These results thus indicate that the miR-145/KLF4/PTBP1/PKMs axis is one of the critical pathways that maintain the Warburg effect in BC carcinogenesis. MiR-145 perturbed the Warburg effect by suppressing the KLF4/PTBP1/PKMs pathway in BC cells, resulting in significant cell growth inhibition.

Original languageEnglish
Pages (from-to)33064-33077
Number of pages14
JournalOncotarget
Volume8
Issue number20
DOIs
Publication statusPublished - 01-01-2017
Externally publishedYes

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Urinary Bladder Neoplasms
MicroRNAs
Critical Pathways
3' Untranslated Regions
Gene Silencing
Growth
Luciferases
Transfection
Neoplasms
Carcinogenesis
Western Blotting
Immunohistochemistry
Apoptosis
Cell Line
Genes

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Minami, K., Taniguchi, K., Sugito, N., Kuranaga, Y., Inamoto, T., Takahara, K., ... Azuma, H. (2017). MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells. Oncotarget, 8(20), 33064-33077. https://doi.org/10.18632/oncotarget.16524
Minami, Koichiro ; Taniguchi, Kohei ; Sugito, Nobuhiko ; Kuranaga, Yuki ; Inamoto, Teruo ; Takahara, Kiyoshi ; Takai, Tomoaki ; Yoshikawa, Yuki ; Kiyama, Satoshi ; Akao, Yukihiro ; Azuma, Haruhito. / MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells. In: Oncotarget. 2017 ; Vol. 8, No. 20. pp. 33064-33077.
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Minami, K, Taniguchi, K, Sugito, N, Kuranaga, Y, Inamoto, T, Takahara, K, Takai, T, Yoshikawa, Y, Kiyama, S, Akao, Y & Azuma, H 2017, 'MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells', Oncotarget, vol. 8, no. 20, pp. 33064-33077. https://doi.org/10.18632/oncotarget.16524

MiR-145 negatively regulates Warburg effect by silencing KLF4 and PTBP1 in bladder cancer cells. / Minami, Koichiro; Taniguchi, Kohei; Sugito, Nobuhiko; Kuranaga, Yuki; Inamoto, Teruo; Takahara, Kiyoshi; Takai, Tomoaki; Yoshikawa, Yuki; Kiyama, Satoshi; Akao, Yukihiro; Azuma, Haruhito.

In: Oncotarget, Vol. 8, No. 20, 01.01.2017, p. 33064-33077.

Research output: Contribution to journalArticle

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AU - Minami, Koichiro

AU - Taniguchi, Kohei

AU - Sugito, Nobuhiko

AU - Kuranaga, Yuki

AU - Inamoto, Teruo

AU - Takahara, Kiyoshi

AU - Takai, Tomoaki

AU - Yoshikawa, Yuki

AU - Kiyama, Satoshi

AU - Akao, Yukihiro

AU - Azuma, Haruhito

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AB - The Warburg effect is a well-known feature in cancer-specific metabolism. We previously reported on the role of microRNA (miR)-145 as a tumor-suppressor in human bladder cancer (BC) cells. In this study, we reveal that miR-145 decreases the Warburg effect by silencing KLF4 in BC cells. The expression levels of miR-145 were significantly lower in clinical BC samples and BC cell lines compared to those in normal tissues and HUC cells. Luciferase assay results showed that miR-145 directly bound to 3'UTR of KLF4, which was shown to be overexpressed in the clinical BC samples using Western blot analysis and immunohistochemistry. Remarkable growth inhibition and apoptosis were induced by the ectopic expression of miR-145 or by the gene silencing of KLF4 (siR-KLF4). Also, Warburg effect-related genes such as PTBP1/PKMs were regulated by the transfection of BC cells with miR-145 or siR-KLF4. These results thus indicate that the miR-145/KLF4/PTBP1/PKMs axis is one of the critical pathways that maintain the Warburg effect in BC carcinogenesis. MiR-145 perturbed the Warburg effect by suppressing the KLF4/PTBP1/PKMs pathway in BC cells, resulting in significant cell growth inhibition.

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