Abstract
Metastatic prostate cancer is the leading cause of morbidity and mortality in men. In this study, we found that expression level of SFMBT2 is altered during prostate cancer progression and has been associated with the migration and invasion of prostate cancer cells. The expression level of SFMBT2 is high in poorly metastatic prostate cancer cells compared to highly metastatic prostate cancer cells. We also found that SFMBT2 knockdown elevates MMP-2, MMP-3, MMP-9, and MMP-26 expression, leading to increased cell migration and invasion in LNCaP and VCaP cells. SFMBT2 interacts with YY1, RNF2, N-CoR and HDAC1/3, as well as repressive histone marks such as H3K9me2, H4K20me2, and H2AK119Ub which are associated with transcriptional repression. In addition, SFMBT2 knockdown decreased KAI1 gene expression through up-regulation of N-CoR gene expression. Expression of SFMBT2 in prostate cancer was strongly associated with clinicopathological features. Patients having higher Gleason score (≥ 8) had substantially lower SFMBT2 expression than patients with lower Gleason score. Moreover, tail vein or intraprostatic injection of SFMBT2 knockdown LNCaP cells induced metastasis. Taken together, our findings suggest that regulation of SFMBT2 may provide a new therapeutic strategy to control prostate cancer metastasis as well as being a potential biomarker of metastatic prostate cancer.
Highlights
The number of newly diagnosed prostate cancer patients has decreased slightly, but newly diagnosed patients in the United States is more than 200,000 cases per year [1]
The expression level of SFMBT2 was high in normal RWPE-1 prostate cells and poorly metastatic LNCaP prostate cancer cells, but low in highly metastatic prostate cancer cells, such as PC3 and DU145, indicating that SFMBT2 expression is likely related to metastasis (Figure 1A)
When SFMBT2 knockdown LNCaP cells were subjected to cell migration assay using a modified Boyden chamber, we found increased cell migration as compared to control siRNA-transfected cells (Figure 1C)
Summary
The number of newly diagnosed prostate cancer patients has decreased slightly, but newly diagnosed patients in the United States is more than 200,000 cases per year [1]. It has been reported that 4% of prostate cancer patients in the United State develop a distant metastasis, but the 5-year survival rate is only 28% compared to. Up-regulation of the Akt/mTOR pathway by inactivation of PTEN is associated with invasion and metastasis of prostate cancer, which has led to development of drugs to inhibit this pathway [10, 11]. Increased expression of matrix metalloproteinases (MMPs) has been shown to be associated with prostate cancer progression and metastasis [11, 12]
Sign-in/Register to view highlights & summary 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.
