Abstract
TSPX is a tumor suppressor gene located at Xp11.22, a prostate cancer susceptibility locus. It is ubiquitously expressed in most tissues but frequently downregulated in various cancers, including lung, brain, liver and prostate cancers. The C-terminal acidic domain (CAD) of TSPX is crucial for the tumor suppressor functions, such as inhibition of cyclin B/CDK1 phosphorylation and androgen receptor transactivation. Currently, the exact role of the TSPX CAD in transcriptional regulation of downstream genes is still uncertain. Using different variants of TSPX, we showed that overexpression of either TSPX, that harbors a CAD, or a CAD-truncated variant (TSPX[∆C]) drastically retarded cell proliferation in a prostate cancer cell line LNCaP, but cell death was induced only by overexpression of TSPX. Transcriptome analyses showed that TSPX or TSPX[∆C] overexpression downregulated multiple cancer-drivers/oncogenes, including MYC and MYB, in a CAD-dependent manner and upregulated various tumor suppressors in a CAD-independent manner. Datamining of transcriptomes of prostate cancer specimens in the Cancer Genome Atlas (TCGA) dataset confirmed the negative correlation between the expression level of TSPX and those of MYC and MYB in clinical prostate cancer, thereby supporting the hypothesis that the CAD of TSPX plays an important role in suppression of cancer-drivers/oncogenes in prostatic oncogenesis.
Highlights
Prostate cancer is one of the leading cancer in the world [1]; more than 200,000 cases are newly diagnosed every year in the United States [2]
To verify the preliminary results of Quantitative reverse-transcription polymerase chain reaction analysis (qRT-PCR) analysis, we had datamined the RNA-Seq gene expression data of clinical prostate cancer samples downloaded from the Cancer Genome Atlas (TCGA) [33]
Of the 52 cases with tumor and non-tumor paired samples, TSPX was downregulated in 44 cases (83%) of prostate cancer, as compared to the adjacent normal specimens, and was up-regulated in 6 cases (11%) (Figure 1B and Table 1), indicating that TSPX was significantly downregulated in prostate cancer of TCGA dataset (Wilcoxon matched pair test P-value < 0.0001)
Summary
Prostate cancer is one of the leading cancer in the world [1]; more than 200,000 cases are newly diagnosed every year in the United States [2]. Recent studies have suggested the involvements of various X-linked tumor suppressors in the prostate cancer development [5,6,7]. A prostate cancer susceptibility locus (loci) has been mapped on Xp11.2 associated with the SNP rs5945572 [8], adjacent of which multiple tumor suppressor genes, including FOXP3 and AMER1 ( known as WTX and FAM123B), are located [7, 9, 10]. FOXP3 is frequently downregulated or inactivated by a mutation(s) in prostate cancer, and reactivation of FOXP3 expression suppresses cancer www.oncotarget.com growth [10, 11]. Mutations in the AMER1 gene are frequently detected in male colorectal cancer [12], its status with prostate cancer is uncertain. Alterations of X-linked genes, tumor suppressors, could play important roles in prostate cancer initiation and progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
