The cover for issue 15 of Oncotarget features Figure 6, "A schematic diagram illustrating the likely mechanism(s) of the TSPX-mediated suppression of the MYC gene," by Kido, et al.
Using different variants of TSPX, we showed that overexpression of either TSPX, that harbors a CAD, or a CAD-truncated variant drastically retarded cell proliferation in a prostate cancer cell line LNCa P, but cell death was induced only by overexpression of TSPX. Datamining of transcriptomes of prostate cancer specimens in the Cancer Genome Atlas 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.
"Prostate cancer is one of the leading cancer in the world; more than 200,000 cases are newly diagnosed every year in the United States."
TSPX is ubiquitously expressed in normal tissues, but it is frequently downregulated in various types of cancer, including lung cancer, glioma, and liver cancer.
Figure 6: A schematic diagram illustrating the likely mechanism(s) of the TSPX-mediated suppression of the MYC gene. TSPX interacts with the MYC promoter region via its SET/NAP domain, and the C-terminal acidic domain (CAD) plays an important role to suppress the MYC gene, likely by recruiting co-repressors to the promoter. Other cancer-drivers/oncogenes that were downregulated by TSPX may be also regulated in the similar manner(s).
TSPX overexpression represses the expression of AR target genes, including KLK2 and KLK3, in a prostate cancer cell line LNCa P.
To explore the above issues, we have examined the effects of overexpression of the full length and variant versions of TSPX in the prostate cancer cell line LNCa P, and determined the respective effects in cell viability, morphology and gene expression patterns using RNA-Seq strategy.
The expression patterns were then compared with those of clinical prostate cancer specimens with high or low TSPX expression from the Cancer Genome Atlas dataset.
Our findings suggest that TSPX is a crucial X-linked tumor suppressor in prostate cancer and its CAD plays important roles in the downregulation of multiple cancer-drivers/oncogenes, and are novel targets for diagnosis and clinical treatment of prostate cancer.
"Prostate cancer is highly heterogeneous cancer with significant variation in disease progression and mortality rate among the patients."
Full text - https://doi.org/10.18632/oncotarget.26673
Correspondence to - Yun-Fai Chris Lau - [email protected]
Keywords - prostate cancer, tumor suppressor, oncogene, transcriptome analyses, TCGA
