SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells

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.

Discovery and development of differentially methylated regions in human papillomavirus‐related oropharyngeal squamous cell carcinoma

“…HOXB4, as a hematopoietic transcription factor, downregulates the expression of Prdm16, which is a proto‐oncogene necessary for self‐renewal and maintenance of murine hematopoietic stem cells . The other eight frequently methylated candidates (CCDC181, DPP4, BEND4, CTNND2, ELMO1, SFMBT2, C1QL3, MIR129–2) confirmed in our study have also shown hypermethylation in other malignancies (Table ) . Among them, SFMBT2 and MIR129–2 have been shown to act as tumor suppressors.…”

“…Among them, SFMBT2 and MIR129–2 have been shown to act as tumor suppressors. SFMBT2 negatively regulates migration and invasion by targeting MMP‐9 and MMP‐26 . MIR129–2 suppresses migration and invasion by directly inhibiting HMGB1 .…”

“…33 The other eight frequently methylated candidates (CCDC181, DPP4, BEND4, CTNND2, ELMO1, SFMBT2, C1QL3, MIR129-2) confirmed in our study have also shown hypermethylation in other malignancies (Table 1). [34][35][36][37][38][39][40][41][42] Among them, SFMBT2 and MIR129-2 have been shown to act as tumor suppressors. SFMBT2 negatively regulates migration and invasion by targeting MMP-9 and MMP-26.…”

TRPM2 promotes the proliferation and invasion of pancreatic ductal adenocarcinoma

“…Lee et al ( 33 ) demonstrated that transcriptional repression was associated with human SFMBT2, which binds preferentially to methylated histone H3 and H4. In addition, it has been revealed that SFMBT2 regulates cell proliferation via epigenetic regulation of homeobox B13 gene expression in the DU145 prostate cancer cell line ( 34 ).…”

Structural basis for EPC1-mediated recruitment of MBTD1 into the NuA4/TIP60 acetyltransferase complex

“…Chromatin-enriched extracts were prepared as described before (Gwak et al, 2016). Briefly, U2OS cells were transfected with WT MBTD1-3xFlag, MBTD1-A236D/L259D/L263D-3xFlag mutant or an empty vector (4µg) using Lipofectamine 2000.…”