Promoter <scp>DNA</scp> methylation is associated with <i>KLF11</i> expression in epithelial ovarian cancer

Wang, Guan; Li, Xianfeng; Tian, Wei; Wang, Yan; Wu, Dandan; Sun, Zhen; Zhao, Ermi

doi:10.1002/gcc.22257

Cited by 19 publications

(12 citation statements)

References 42 publications

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“…A number of studies demonstrated that DNA methylation in gene promoters can suppress gene transcriptional activity and results in downregulated gene expression (Baubec et al., ; Hallberg et al., ; Wang et al., ). Our previous studies showed that mRNA expression of the SC protein FKBP6 is significantly lower in testes of cattle–yak than in testes of yak (Li et al., ).…”

Section: Discussionmentioning

confidence: 99%

Differential DNA methylation of the meiosis‐specific gene FKBP6 in testes of yak and cattle–yak hybrids

Luo

Weng

et al. 2016

Reprod Domestic Animals

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FK506-binding protein 6 (FKBP6) is essential for meiosis during mammalian spermatogenesis. However, the molecular regulation of FKBP6 during spermatogenesis remains unclear. In the present study, we performed molecular characterization of the meiosis-specific gene FKBP6 in yak testes. Yak FKBP6 encodes a polypeptide of 295 amino acid residues with an FK506-binding domain (FKBP_C) and three tetratricopeptide repeat domains. The methylation level of the FKBP6 promoter in testes was significantly higher in cattle-yak with male sterility than in yak, and the FKBP6 promoter was methylated in liver tissues in which FKBP6 is not expressed. FKBP6 promoter activity was significantly decreased after treatment with the M.SssI methyltransferase in vitro. Furthermore, the FKBP6 gene was remarkably activated in bovine mammary epithelial cells treated with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine. Taken together, our results demonstrate for the first time that the FKBP6 promoter is differentially methylated in testes; together with the functional promoter analysis, this suggests that methylation of this promoter may contribute to cattle-yak male infertility.

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Section: Discussionmentioning

confidence: 99%

Differential DNA methylation of the meiosis‐specific gene FKBP6 in testes of yak and cattle–yak hybrids

Luo

Weng

et al. 2016

Reprod Domestic Animals

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“…*p<0.05 and co-repressors [14,15]. In previous studies, KLF11 supported TGF-β signaling by terminating the smad7 loop and activating smad3; thus exerting anti-proliferative and pro-apoptotic functions in epithelial ovarian, pancreatic and liver cancer cells [17][18][19][20]. In the process of TGF-βinduced EMT, KLF11 significantly promoted hepatocellular carcinoma local invasion and distant metastasis by binding to the Smad7 promoter and suppressing transcription of Smad7 or directly up-regulating Smad2/3 expression [21,23].…”

Section: Discussionmentioning

confidence: 93%

“…KLF11 is a member of this family and contains three C 2 H 2 -type zinc fingers, 2 acids and 2 regions rich in proline at the carboxyl and amino terminals [16]. Previous studies have shown that KLF11 has significant influence on proliferation, differentiation and apoptosis in epithelial ovarian, pancreatic and liver cancer [17][18][19][20]. While KLF11 promotes local invasion and distant migration in the EMT process in hepatocellular carcinoma [21], its biological functions and relationship with EMT in gastric cancer are not clarified.…”

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confidence: 99%

KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression

Zhao

et al. 2019

neo

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Gastric cancer (GC) is a leading cause of global cancer-related death. The incidence and mortality rates of gastric cancer in China are second and third ranked in all forms of malignant tumors. Krüppel-like factor11 (KLF11) is a member of the KLF family, and previous studies have shown it significantly influences epithelial ovarian, pancreatic and liver cancer proliferation, differentiation and apoptosis. However, the expression and some biological functions of KLF11 in GC are still unclear. We therefore collected and analyzed the mRNA and protein expressions of KLF11 in 59 paired gastric cancer tissues and matched healthy gastric tissue samples. We then investigated the KLF 11 biological functions and potential mechanisms in BGC823 and HGC27 gastric cancer cell lines. Analysis of KLF11 in gastric cancer specimens confirmed up-regulation compared to adjacent healthy gastric tissues, and similar results were evident in the GC cell lines. Ectopic expression of KLF11 was significantly associated with GC cell invasion and migration. KLF11 functions were most effective in Twist1 expression and knockdown, and also in KLF11 up-regulation which was accompanied by corresponding change in Twist1 expression; but these effects were inhibited when KLF11 was silenced by the small interfering RNA (siRNA). The relative Twist1 promoter region activity increased gradually with increasing KLF11 plasma, and KLF11 therefore has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression. Finally, the results of this study should improve understanding of the KLF11 and EMT regulating network and KLF11's use as a potential therapeutic target in gastric cancer.

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“…They also investigated the methylation level between normal and tumor ovarian tissues in 31 Chinese patients. Compared with the normal samples, the overall methylation level was dramatically increased in the tumor tissues (P = 0.0001), and this significant difference was observed through all stages of the disease (G. Wang et al, 2015). In another study, Potapova et al demonstrated that epigenetic inactivation of KLF11 occurs in myelodysplastic syndrome.…”

Section: Discussionmentioning

confidence: 95%

The Methylation Analysis of KLF11 and PCDH9 Genes in Patients with Non-Small Cell Lung Cancer

Nooshin¹,

Karizi²,

Karimipoor³

et al. 2018

CCO

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Background: Lung cancer is the leading cause of cancer-related deaths worldwide and the 5-year survival rate is still very poor due to the lack of effective tools for early detection. Epigenetics and especially studies on DNA methylation have given important information towards a better achievement of lung cancer pathogenesis in the recent decades. The inactivation of tumor suppressor genes via promoter hypermethylation is an obvious mechanism and is straightly related to carcinogenesis. In this study, we compared the methylation status of KLF11 and PCDH9 genes in non-small cell lung cancer and adjacent normal tissues.Methods: Genomic DNA was extracted from 30 tumor tissues, bisulfite treated and were analyzed in terms of promoter methylation status of KLF11 and PCDH9 genes by high resolution melting method. Statistical analysis was carried out by chi-square test.Results: No significant difference in methylation level at the PCDH9 promoter region in NSCLC tumors compared with non-tumor tissues was observed (P = 0.3132, chi-square test). In contrast, the difference in methylation levels between normal and tumor tissue samples for the promoter of the KLF11 gene was quite significant (P = 0.0001).Conclusions: Promoter methylation of KLF11 gene is an important mechanism in the development of NSCLC, therefore, it could be used as one of the potential therapeutic goals for molecular targeted therapy and epigenetic treatment. The role of the PCDH9 gene in the development of lung cancer is complex and requires more research and a larger statistical population.

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Promoter DNA methylation is associated with KLF11 expression in epithelial ovarian cancer

Cited by 19 publications

References 42 publications

Differential DNA methylation of the meiosis‐specific gene FKBP6 in testes of yak and cattle–yak hybrids

Differential DNA methylation of the meiosis‐specific gene FKBP6 in testes of yak and cattle–yak hybrids

KLF11 promotes gastric cancer invasion and migration by increasing Twist1 expression

The Methylation Analysis of KLF11 and PCDH9 Genes in Patients with Non-Small Cell Lung Cancer

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