Histone methyltransferase SUV39H2 serves oncogenic roles in osteosarcoma

Abstract

Suppressor of variegation 3-9 homologue 2 (SUV39H2), a SET domain-containing histone methyltransferase, trimethylates histone H3 at lysine 9 and serves crucial roles in heterochromatin organization and genome stability. SUV39H2 is overexpressed in various types of human cancer, whereas it is almost undetectable in normal adult tissues, except testis. The aim of this study was to investigate a potential role of SUV39H2 in osteosarcoma. In the present study, increased SUV39H2 expression levels were observed in osteosarcoma, the most common primary bone cancer in children and adolescents, and the knockdown of SUV39H2 expression by specific small interfering RNAs in osteosarcoma cells markedly suppressed cancer cell growth and led to a notable reduction in cell viability. Furthermore, overexpression of SUV39H2 promoted cell proliferation, which indicated that SUV39H2 may possess oncogenic activity in human osteosarcoma. Notably, depletion of SUV39H2 expression caused an increase in the population of G1 phase and induced apoptosis, which implied that SUV39H2 may have biological significance in the process of cell cycle. These results indicated that SUV39H2 may be an ideal target for osteosarcoma therapeutics.

RETRACTED ARTICLE: Histone methyltransferase SUV39H2 regulates LSD1-dependent CDH1 expression and promotes epithelial mesenchymal transition of osteosarcoma

“…Consistent with our research findings, the expression of SUV39H2 is significantly upregulated in OS, whereas depletion of SUV39H2 expression by specific small interfering RNA could dramatically suppress the growth of OS cells, leading to a significant decrease in cell survival rate [9]. In our subsequent experiments, we found that SUV39H2 promotes EMT and migration of OS cells.…”

“…Histone methyltransferases such as SETD2 are significantly implicated in OS [7]. Moreover, histone methyltransferase SUV39H2 reportedly can promote the occurrence and progression of OS [9]. Therefore, we aimed in this study to investigate the mechanism whereby SUV39H2 affects OS by meditation of the LSD1/CDH1 axis.…”

“…SUV39H2 has been reported to promote the development of OS [9]. We conducted this study to explore the potential mechanism of SUV39H2 in OS.…”

“…Suppressor of variegation 3-9 homolog 2 (SUV39H2), a member of the lysine methyltransferase SUV39 subfamily, acts by influencing the degree of H3K9 methylation, transcriptional regulation, and cell cycle [8]. SUV39H2 promotes the development of OS, given that SUV39H2 expression is significantly upregulated in OS, whereas the depletion of SUV39H2 expression by specific small interfering RNAs can dramatically suppress the growth of OS cells, leading to a significant decrease in cell survival rate [9]. Furthermore, SUV39H2 can stabilize and elevate the expression of lysine specific demethylase-1 (LSD1) by virtue of its intrinsic methylating enzyme function, such that downregulation of SUV39H2 contributes to the reduction of LSD1 protein expression [10].…”

Sequencing two Tyr::CreERT2 transgenic mouse lines

“…Suv39h2 is a histone‐lysine N‐methyltransferase, which is involved primarily in the tri‐methylation of Lysine9 on Histone H3, leading to transcriptional repression (O'Carroll et al, ). While overexpression of Suv39h2 is observed in various cancer types (including colorectal cancer, osteosarcoma, and leukemia) and it is thought to promote tumorigenesis (Carvalho Alves‐Silva et al, ; Piao et al, ; Shuai et al, ), it has no documented role in melanoma, and the expression in melanoma is very low (Rambow et al, ). Importantly, the read‐depth analysis showed that the Suv39h2 gene was present at normal levels (i.e., 2n) in the Tyr::CreER T2‐Lar mice.…”