Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration

Chen, Libo

doi:10.3748/wjg.v13.i43.5718

Cited by 40 publications

(40 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it is possible that the suppression of TE-specific genes, such as Cdx2 and Eomes, could account for a defect in the ability of Smyd3-knockdown embryos to attach to a matrix substrate in vitro. Furthermore, it has been reported that Smyd3 knockdown induces apoptosis in cancer (Chen et al 2007). In the present study, however, we showed that the number of apoptotic cells was not increased in Smyd3-knockdown embryos.…”

Section: Role Of Smyd3 In Embryonic Lineage Commitmentcontrasting

confidence: 87%

“…Because it has been reported that Smyd3 knockdown induces apoptosis in human cancer cells (Chen et al 2007), we investigated the effects of Smyd3 knockdown on apoptosis in mouse peri-implantation embryos. However, there was no difference in the number of TUNEL-positive cells between Smyd3-knockdown and control embryos (Fig.…”

Section: Knockdown Of Smyd3 Does Not Induce Apoptosis During Peri-impmentioning

confidence: 99%

“…Evidence has accumulated that suggests that SMYD3 recruits RNA polymerase II through an RNA helicase to form a transcription complex and that it elicits its oncogenic effects by activating the transcription of downstream target genes (Hamamoto et al 2004, 2006, Liu et al 2007. Previous reports have demonstrated that enhanced expression of SMYD3 is essential for the growth of human cancer cells (Hamamoto et al 2004(Hamamoto et al , 2006, whereas the suppression of SMYD3 expression leads to apoptosis and the inhibition of cell growth, migration, and invasion (Chen et al 2007, Zou et al 2009). Recent studies have determined that Smyd3 plays an important role in the development of heart and skeletal muscle during zebrafish embryogenesis (Fujii et al 2011).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice

Suzuki¹,

Nozawa²,

Tsukamoto³

et al. 2015

Reproduction

View full text Add to dashboard Cite

SET and MYND domain-containing protein 3 (Smyd3) is a histone H3 lysine 4 (H3K4) di-and tri-methyltransferase that forms a transcriptional complex with RNA polymerase II and activates the transcription of oncogenes and cell cycle genes in human cancer cells. However, the study of Smyd3 in mammalian early embryonic development has not yet been addressed. In the present study, we investigated the expression pattern of Smyd3 in mouse preimplantation embryos and the effects of RNA interference (RNAi)-mediated Smyd3 repression on the development of mouse embryos. We showed that Smyd3 mRNA levels increased after the two-cell stage, peaked at the four-cell stage, and gradually decreased thereafter. Moreover, in two-cell to eight-cell embryos, SMYD3 staining was more intense in the nuclei than it was in the cytoplasm. In Smyd3-knockdown embryos, the percentage of inner cell mass (ICM)-derived colony formation and trophectoderm (TE)-derived cell attachment were significantly decreased, which resulted in a reduction in the number of viable offspring. Furthermore, the expression of Oct4 and Cdx2 during mid-preimplantation gene activation was significantly decreased in Smyd3-knockdown embryos. In addition, the transcription levels of ICM and epiblast markers, such as Oct4, Nanog, and Sox2, the transcription levels of primitive endoderm markers, such as Gata6, and the transcription levels of TE markers, such as Cdx2 and Eomes, were significantly decreased in Smyd3-knockdown blastocysts. These findings indicate that SMYD3 plays an important role in early embryonic lineage commitment and peri-implantation development through the activation of lineage-specific genes.Reproduction (2015) 150 21-30

show abstract

Section: Role Of Smyd3 In Embryonic Lineage Commitmentcontrasting

confidence: 87%

Section: Knockdown Of Smyd3 Does Not Induce Apoptosis During Peri-impmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice

Suzuki¹,

Nozawa²,

Tsukamoto³

et al. 2015

Reproduction

View full text Add to dashboard Cite

show abstract

“…The abnormal expression of RIZ1 is associated with the tumorigenesis of a variety of human tumors, including nasopharyngeal, breast, liver and cervical among other cancers (16,17). Nomoto et al (18) reported that the frequency of RIZ1 gene methylation was 45.2% among patients with HCC in Japan.…”

Section: Gstp1 Methylation P16 Methylation --------------------------mentioning

confidence: 99%

Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance

Jiang

et al. 2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. Hepatocellular carcinoma (HCC) has a high rate of mortality. Further studies into epigenetic changes in HCC, particularly the abnormal methylation of tumor suppressor genes (TSGs), are required, since these changes may provide novel biomarkers for early screening and diagnosis of HCC. By using methylation-specific polymerase chain reaction (MSP), the present study detected the methylation status in the promoter region of 4 candidate TSGs, GSTP1, P16, RIZ1, and RASSF1A, respectively, in 35 paired HCC and tumor-adjacent liver tissues in addition to 20 normal liver tissues. Their effect on the initiation and progression of HCC was also investigated by analyzing the clinicopathological data. The results of the present study revealed that the methylation level of RIZ1 and GSTP1 genes in HCC was significantly increased compared with that in the adjacent tissues (P<0.01) and the normal liver tissues (P<0.01). The methylation frequency of P16 and RASSF1A genes was not significantly increased compared with that observed in the adjacent tissues (P>0.05) but was significantly increased compared with the normal tissues (P<0.01). In HCC tissues, the methylation frequency of the GSTP1 gene in tumors with capsular invasion was significantly increased compared with that in tumors without capsular invasion (P<0.05). The methylation frequency of P16 gene in hepatitis B surface antigen (HbsAg)-positive HCC patients was significantly increased compared with that in HbsAg-negative patients (P<0.05). The methylation status of RIZ1 and RASSF1A genes was not significantly correlated with the clinicopathological data (P>0.05). Previous studies have demonstrated that the methylation status of RIZ1 and GSTP1 genes is HCC-specific, and thus may be used as a biomarker to assist the clinical diagnosis of HCC. While the methylation of GSTP1 gene promoter may associate with the invasiveness of HCC, chronic hepatitis B virus infection may be the cause of methylation-induced P16 inactivation. IntroductionHCC is one of the tumors with the highest incidence worldwide, and its incidence and mortality in China have remained high. The occurrence of HCC is results from multiple factors, including the activation of certain oncogenes, inactivation of TSGs and exogenous stimuli. Previous studies have demonstrated that the hypermethylation of CpG islands in tumor suppressor gene (TSG) promoters is closely associated with the formation of HCC, which may transform the spatial structure of chromatin and hence block/silence the transcription of TSGs via recruiting proteins of the methyl CpG binding domain (MBD) family in addition to the associated protein complexes (1,2). Epigenetic silencing is a relatively common mechanism of TSG inactivation (3). The aberrant methylation of tumor-associated genes, particularly TSGs, requires further research.A high frequency of methylation inactivation of the GSTP1 gene has been observed in human prostate, kidney, and liver cancers (4-6). Zhang et al (7) and Tchou et al (8) demonstrated that there is a high freq...

show abstract

“…Hepatocellular carcinoma (HCC) research has shown that RNAi targeting genes are related to initiation, development and metastasis of HCC [2][3][4] . Signal transducer and activator of transcription 3 (STAT3) is an important member of the family of STAT.…”

Section: Introductionmentioning

confidence: 99%

Silencing of signal transducer and activator of transcription 3 expression by RNA interference suppresses growth of human hepatocellular carcinoma in tumor-bearing nude mice

Piao²,

Jiang³

et al. 2009

WJG

View full text Add to dashboard Cite

AIM:To explore the effect of silencing of signal transducer and activator of transcription 3 (STAT3) expression by RNA interference (RNAi) on growth of human hepatocellular carcinoma (HCC) in tumorbearing nude mice in vivo . METHODS:To construct the recombinant plasmid of pSilencer 3.0-H1-STAT3-siRNA-GFP (pSH1-siRNA-STAT3) and establish the tumor-bearing nude mouse model of the HCC cell line SMMC7721, we used intratumoral injection together with electroblotting to transfect the recombinant plasmid pSH1-siRNA-STAT3 into the transplanted tumor. The weight of the nude mice and tumor volumes were recorded.

show abstract

Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration

Cited by 40 publications

References 25 publications

Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice

Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice

Detecting abnormal methylation of tumor suppressor genes GSTP1, P16, RIZ1, and RASSF1A in hepatocellular carcinoma and its clinical significance

Silencing of signal transducer and activator of transcription 3 expression by RNA interference suppresses growth of human hepatocellular carcinoma in tumor-bearing nude mice

Contact Info

Product

Resources

About