Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas

Yasushi Matsuyama, Motoshi Suzuki, Chinatsu Arima, Qin Miao Huang, Shuta Tomida, Toshiyuki Takeuchi, Ryoji Sugiyama, Yasutomo Itoh, Yasushi Yatabe, Hidemi Goto, Takashi Takahashi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We previously identified PSMD2, a subunit of the 19S regulatory complex of proteasomes, as a constituent of a signature associated with the acquisition of metastatic phenotype and poor prognosis in lung cancers. In the present study, we found that knockdown of PSMD2 decreased proteasome activity, and induced growth inhibition and apoptosis in lung cancer cell lines. These effects of siRNA-mediated PSMD2 inhibition were associated with changes in the balance between phosphorylated AKT and p38, as well as with induction of p21. In addition, patients with higher PSMD2 expression had poorer prognosis and a small fraction of lung cancer specimens carried increased copies of PSMD2. Notably, our findings clearly illustrate that lung adenocarcinomas can be divided into two groups; those with and without general upregulation of proteasome pathway genes including PSMD2. This general upregulation was significantly more prevalent in the non-terminal respiratory unit (non-TRU)-type, a recently proposed genetically and clinicopathologically relevant expression profile-defined classification of adenocarcinomas (P<0.001 by Fisher's exact test). Patients with adenocarcinomas with general upregulation had significantly shorter survival after potentially curative resection (P=0.0001 by log-rank test) independent of disease stage, as shown by multivariate Cox regression analysis. Our results suggest that PSMD2 may be a good molecular target candidate and that other co-regulated proteasome pathway genes and/or their common regulator(s) might also be potential targets, warranting future study including elucidation of the underlying common regulatory mechanism.

Original languageEnglish
Pages (from-to)301-309
Number of pages9
JournalMolecular Carcinogenesis
Volume50
Issue number4
DOIs
Publication statusPublished - 01-04-2011

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Proteasome Endopeptidase Complex
Lung Neoplasms
Up-Regulation
Adenocarcinoma
Therapeutics
Small Interfering RNA
Genes
Regression Analysis
Apoptosis
Phenotype
Cell Line
Survival
Adenocarcinoma of lung
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Matsuyama, Yasushi ; Suzuki, Motoshi ; Arima, Chinatsu ; Huang, Qin Miao ; Tomida, Shuta ; Takeuchi, Toshiyuki ; Sugiyama, Ryoji ; Itoh, Yasutomo ; Yatabe, Yasushi ; Goto, Hidemi ; Takahashi, Takashi. / Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas. In: Molecular Carcinogenesis. 2011 ; Vol. 50, No. 4. pp. 301-309.
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Matsuyama, Y, Suzuki, M, Arima, C, Huang, QM, Tomida, S, Takeuchi, T, Sugiyama, R, Itoh, Y, Yatabe, Y, Goto, H & Takahashi, T 2011, 'Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas', Molecular Carcinogenesis, vol. 50, no. 4, pp. 301-309. https://doi.org/10.1002/mc.20632

Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas. / Matsuyama, Yasushi; Suzuki, Motoshi; Arima, Chinatsu; Huang, Qin Miao; Tomida, Shuta; Takeuchi, Toshiyuki; Sugiyama, Ryoji; Itoh, Yasutomo; Yatabe, Yasushi; Goto, Hidemi; Takahashi, Takashi.

In: Molecular Carcinogenesis, Vol. 50, No. 4, 01.04.2011, p. 301-309.

Research output: Contribution to journalArticle

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AU - Matsuyama, Yasushi

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AU - Huang, Qin Miao

AU - Tomida, Shuta

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AU - Sugiyama, Ryoji

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