MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer

Koichiro Saito, Koji Inagaki, Takahiro Kamimoto, Yoko Ito, Toshiaki Sugita, Satoko Nakajo, Akira Hirasawa, Arifumi Iwamaru, Takashi Ishikura, Hideki Hanaoka, Keisuke Okubo, Tokio Onozaki, Takeru Zama

Research output: Contribution to journalArticle

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Abstract

Background:MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the role of miRNAs as ideal biomarkers and therapeutic targets due to their tissue- or disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, and laryngeal cancer has the highest incidence in it. However, the molecular mechanisms involved in laryngeal cancer development remain to be known and highly sensitive biomarkers and novel promising therapy is necessary.Methodology/Principal Findings:To explore laryngeal cancer-specific miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer tissues were hybridized to microarray carrying 723 human miRNAs. The resultant differentially expressed miRNAs were further tested by using quantitative real time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous counterparts, benign diseases and precancerous dysplasias. Significant expressional differences between matched pairs were reproduced in miR-133b, miR-455-5p, and miR-196a, among which miR-196a being the most promising cancer biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep sequencing analysis revealed both quantitative and qualitative deviation of miR-196a isomiR expression in laryngeal cancer. In situ hybridization confirmed laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in both laryngeal cancer-derived cells and mouse xenograft model.Conclusions/Significance:Our study provided the possibilities that miR-196a might be very useful in diagnosing and treating laryngeal cancer.

Original languageEnglish
Article numbere71480
JournalPLoS One
Volume8
Issue number8
DOIs
Publication statusPublished - 2013 Aug 14

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Laryngeal Neoplasms
Biomarkers
MicroRNAs
microRNA
biomarkers
therapeutics
neoplasms
Tissue
Neoplasms
Therapeutics
Small Untranslated RNA
Real-Time Polymerase Chain Reaction
quantitative polymerase chain reaction
Cell proliferation
Microarrays
Tumor Biomarkers
Physiological Phenomena
Heterografts
Gene expression
High-Throughput Nucleotide Sequencing

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Saito, K., Inagaki, K., Kamimoto, T., Ito, Y., Sugita, T., Nakajo, S., ... Zama, T. (2013). MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer. PLoS One, 8(8), [e71480]. https://doi.org/10.1371/journal.pone.0071480

MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer. / Saito, Koichiro; Inagaki, Koji; Kamimoto, Takahiro; Ito, Yoko; Sugita, Toshiaki; Nakajo, Satoko; Hirasawa, Akira; Iwamaru, Arifumi; Ishikura, Takashi; Hanaoka, Hideki; Okubo, Keisuke; Onozaki, Tokio; Zama, Takeru.

In: PLoS One, Vol. 8, No. 8, e71480, 14.08.2013.

Research output: Contribution to journalArticle

Saito, K, Inagaki, K, Kamimoto, T, Ito, Y, Sugita, T, Nakajo, S, Hirasawa, A, Iwamaru, A, Ishikura, T, Hanaoka, H, Okubo, K, Onozaki, T & Zama, T 2013, 'MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer', PLoS One, vol. 8, no. 8, e71480. https://doi.org/10.1371/journal.pone.0071480
Saito, Koichiro ; Inagaki, Koji ; Kamimoto, Takahiro ; Ito, Yoko ; Sugita, Toshiaki ; Nakajo, Satoko ; Hirasawa, Akira ; Iwamaru, Arifumi ; Ishikura, Takashi ; Hanaoka, Hideki ; Okubo, Keisuke ; Onozaki, Tokio ; Zama, Takeru. / MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer. In: PLoS One. 2013 ; Vol. 8, No. 8.
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