Abstract:
:Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Kato T,Lee D,Wu L,Patel P,Young AJ,Wada H,Hu HP,Ujiie H,Kaji M,Kano S,Matsuge S,Domen H,Kaga K,Matsui Y,Kanno H,Hatanaka Y,Hatanaka KC,Matsuno Y,de Perrot M,Yasufuku Kdoi
10.3892/ijo.2016.3566subject
Has Abstractpub_date
2016-08-01 00:00:00pages
448-56issue
2eissn
1019-6439issn
1791-2423journal_volume
49pub_type
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