Abstract
Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes in WHO°I to °III meningiomas (WHO°I n = 61, WHO°II n = 88, and WHO°III n = 59), which was most pronounced in clinically more aggressive tumors of the same WHO grade. Immunohistochemical staining confirmed a WHO grade-associated upregulated protein expression in meningioma tissues. Furthermore, high mRNA expression levels of KIFC1, KIF11, KIF14 and KIF20A were associated with shorter progression-free survival. On a functional level, knockdown of kinesins in Ben-Men-1 cells and in the newly established anaplastic meningioma cell line NCH93 resulted in a significantly inhibited tumor cell proliferation upon siRNA-mediated downregulation of KIF11 in both cell lines by up to 95% and 71%, respectively. Taken together, in this study we were able to identify the prognostic and functional role of several kinesin family members of which KIF11 exhibits the most promising properties as a novel prognostic marker and therapeutic target, which may offer new treatment options for aggressive meningiomas.
Highlights
Meningiomas (MGMs) are tumors of the central nervous system and account for one-third of all brain tumors
By re-analyzing our dataset for the expression of members of the kinesin family, we identified significant differential gene expression of five kinesins: KIFC1, KIF4A, KIF11, KIF14 and KIF20A (Supplementary Table S3)
Further validation in an extended study sample of 208 cases fairly representing all World Health Organization (WHO) grades revealed a significant upregulation of all investigated kinesins in meningiomas WHO◦ I to ◦ III which even translated into an upregulated protein expression
Summary
Meningiomas (MGMs) are tumors of the central nervous system and account for one-third of all brain tumors. They are assumed to arise from the meningeal coverings of the brain and the spinal cord [1]. Meningiomas are histologically classified according to the World Health Organization’s (WHO) grading scheme [2]. 80% of meningiomas are benign, corresponding to WHO◦ I, 10–15%. Are atypical (WHO◦ II), and only 2–5% are anaplastic meningiomas WHO◦ III. Their incidence ranges from 1.3 per 100,000 to 7.8 per 100,000 [3]. Clinical outcome strongly depends on the WHO grade
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