SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma

Kato,Tatsuya; Lee,Daiyoon; Wu,Licun; Patel,Priya; Young,Ahn Jin; Wada,Hironobu; Hu,Hsin-Pei; Ujiie,Hideki; Kaji,Mitsuhito; Kano,Satoshi; Matsuge,Shinichi; Domen,Hiromitsu; Kanno,Hiromi; Hatanaka,Yutaka; Hatanaka,Kanako C.; Kaga,Kichizo; Matsui,Yoshiro; Matsuno,Yoshihiro; De Perrot,Marc; Yasufuku,Kazuhiro

doi:10.3892/ijo.2016.3765

SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma

Authors:
- Tatsuya Kato
- Daiyoon Lee
- Licun Wu
- Priya Patel
- Ahn Jin Young
- Hironobu Wada
- Hsin-Pei Hu
- Hideki Ujiie
- Mitsuhito Kaji
- Satoshi Kano
- Shinichi Matsuge
- Hiromitsu Domen
- Hiromi Kanno
- Yutaka Hatanaka
- Kanako C. Hatanaka
- Kichizo Kaga
- Yoshiro Matsui
- Yoshihiro Matsuno
- Marc De Perrot
- Kazuhiro Yasufuku
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Affiliations: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Canada, Department of Thoracic Surgery, Sapporo Minami-sanjo Hospital, Sapporo, Japan, Department of Pathology, Kinikyo-Chuo Hospital, Sapporo, Japan, Department of Surgery, Kinikyo-Chuo Hospital, Sapporo, Japan, Department of Cardiovascular and Thoracic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan, Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
Published online on: November 10, 2016 https://doi.org/10.3892/ijo.2016.3765
Pages: 2411-2420

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Abstract

Malignant pleural mesothelioma (MPM) is an aggressive type of cancer of the thoracic cavity commonly associated with asbestos exposure and a high mortality rate. There is a need for new molecular targets for the development of more effective therapies for MPM. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and an RNA interference-based screening, we examined the SORORIN gene as potential therapeutic targets for MPM in addition to the PLK1 gene, which is known for kinase of SORORIN. Following in vitro investigation of the effects of target silencing on MPM cells, cell cycle analyses were performed. SORORIN expression was analyzed immunohistochemically using a total of 53 MPM samples on tissue microarray. SORORIN was found to be overexpressed in the majority of clinical MPM samples and human MPM cell lines as determined by qRT-PCR. Gene suppression of each SORORIN and PLK1 led to growth inhibition in MPM cell lines. Knockdown of SORORIN showed an increased number of G2M-phase population and a larger nuclear size, suggesting mitotic arrest. High expression of SORORIN (SORORIN-H) was found in 50.9% of all the MPM cases, and there is a tendency towards poorer prognosis for the SORORIN-H group but the difference is not significant. Suppression of SORORIN with PLK1 inhibitor BI 6727 showed a combinational growth suppressive effect on MPM cell growth. Given high-dose PLK1 inhibitor induced drug-related adverse effects in several clinical trials, our results suggest inhibition SORORIN-PLK1 axis may hold promise for the treatment of MPMs.

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