EZH2 contributes to 5-FU resistance in gastric cancer by epigenetically suppressing FBXO32 expression

Wang, Chenyu; Li, Xingwang; Zhang, Junjie; Ge, Zheng; Chen, Hejin; Hu, Junhong

doi:10.2147/ott.s180131

Cited by 35 publications

(24 citation statements)

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“…We found through UCSC (http://genome.ucsc.edu/) that NDRG2 promoter contains potential binding sites for EZH2 (Figure 3B). EZH2 is defined as a histone methyltransferase, which can induce histone H3K27me3 on the promoter to result in epigenetic silence of genes (Kim and Roberts, 2016; Wang et al, 2018; Xu et al, 2018). It has been widely reported that lncRNAs could epigenetically repress gene expression by recruiting EZH2 (Zhang and Peng, 2017; Ma et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

“…We predicted via searching UCSC and confirmed through ChIP assay that EZH2 bound to NDRG2 promoter. It is axiomatically known that EZH2 can regulate histone H3K27me3 on the promoter of genes, so as to repress the gene expression (Kim and Roberts, 2016; Wang et al, 2018; Xu et al, 2018). Accordingly, our study first revealed that UNC5B‐AS1 interacted with EZH2 to target NDRG2.…”

Section: Discussionmentioning

confidence: 99%

“…Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is defined as a histone methyltransferase responsible for histone H3 lysine 27 trimethylation (H3K27me3), which induces epigenetic silencing of genes in cancers (Kim and Roberts, 2016; Wang et al, 2018; Xu et al, 2018). In OC, EZH2 is reported to promote the tumor progression by epigenetically silencing anti‐tumor genes, such as TIMP2 and ARNTL (Yeh et al, 2014; Yi et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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UNC5B‐AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2

Wang

Tan

2020

Cell Biology International

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The role of long non‐coding RNAs (lncRNAs) in tumorigenesis and development of ovarian cancer (OC) has caught the attention of scientists. UNC5B antisense RNA 1 (UNC5B‐AS1) is a newly identified carcinogenic lncRNA in thyroid papillary carcinoma, but its role in OC remains unclear. This study is proposed to investigate the function and mechanism of UNC5B‐AS1 in OC. UNC5B‐AS1 expression in OC samples was obtained from gene expression profiling interactive analysis (GEPIA) based on The Cancer Genome Atlas data. Gene expressions were detected by quantitative real‐time polymerase chain reaction (RT‐qPCR) and western blot. Biological functions of UNC5B‐AS1 were assessed by cell counting kit‐8, colony formation, and caspase‐3 analysis. GEPIA revealed the UNC5B‐AS1 upregulation in OC samples. RT‐qPCR assay confirmed the upregulation of UNC5B‐AS1 in OC cells. Functionally, depletion of UCN5B‐AS1 hindered proliferation and prompted apoptosis in OC cells. Mechanistically, we found that UNC5B‐AS1 interacted with zeste 2 polycomb repressive complex 2 subunit (EZH2) to trigger trimethylation of histone H3 at lysine 27 (H3K27me3) on N‐myc downstream regulated gene‐2 (NDRG2) promoter and epigenetically repressed NDRG2. Rescue assay indicated the participation of NDRG2 in the regulation of UNC5B‐AS1 on OC progression. Together, we first illustrated that UNC5B‐AS1 promoted OC progression by regulating the H3K27me on NDRG2 via EZH2, indicating UNC5B‐AS1 as a potential molecular target for OC treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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UNC5B‐AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2

Wang

Tan

2020

Cell Biology International

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“…RPL11, ribosomal protein L11; TP53, Tumor protein p53; 5-FU, 5-fluorouracil; si, small interfering RNA. poor prognosis of gastric cancer patients (27). Although further investigation is needed, gastric cancer patients with both high RPL11 expression and low EZH2 expression may show higher sensitivity against 5-FU treatment than those with either high RPL11 or low EZH2 expression alone, which may help to more accurately predict 5-FU sensitivity in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Involvement of ribosomal protein L11 expression in sensitivity of gastric cancer against 5‑FU

et al. 2020

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5-Fluorouracil (5-FU) is widely used in the treatment of various types of solid cancer. Our study showed that ribosomal protein L11 (RPL11) was a crucial factor affecting sensitivity of gastric cancer to 5-FU, implying that RPL11 expression is a potential biomarker for predicting 5-FU sensitivity. Kaplan-Meier survival analysis indicated that high RPL11 expression in gastric cancer patients treated with 5-FU was significantly associated with good prognosis. It was therefore investigated whether RPL11 affected the sensitivity of gastric cancer against 5-FU using four human gastric cancer cell lines, MKN45 (wild-type TP53 gene), NUGC4 (wild-type), MKN7 (mutated), and KE39 cells (mutated). In vitro assays demonstrated that RPL11 knockdown in gastric cancer cell lines carrying the TP53 wild-type gene attenuated 5-FU-induced cell growth suppression and activation of the P53 pathway, but not in cells carrying mutated TP53, suggesting that 5-FU suppresses tumor progression via RPL11-mediated activation of the P53 pathway in gastric cancer. The present study provides a potential therapeutic strategy for improving 5-FU resistance in gastric cancer by elevating RPL11 expression.

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“…Its expression was clearly downregulated in oral cancer cell lines following miR-629-3p transfection. It has been reported to contribute to CDDP resistance in urothelial cancer and 5-fluorouracil (5-FU) resistance in gastric cancer [21,22]. FBXO32, which is one of the candidates but not confirmed by qRT-PCR, is known to be related to drug resistance.…”

Section: Discussionmentioning

confidence: 99%

CD44s Induces miR-629-3p Expression in Association with Cisplatin Resistance in Head and Neck Cancer Cells

Chikuda

Otsuka²,

Shimomura³

et al. 2020

Cancers

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Cisplatin (cis-diamminedichloroplatinum II [CDDP] ) is a well-known chemotherapeutic drug that has been used for the treatment of various types of human cancers, including head and neck cancer. Cisplatin exerts anticancer effects by causing DNA damage, replication defects, transcriptional inhibition, cell cycle arrest, and the induction of apoptosis. However, drug resistance is one of the most serious problems with cancer chemotherapy, and it causes expected therapeutic effects to not always be achieved. Here, we analyzed global microRNA (miRNA) expression in CD44 standard form (CD44s)-expressing SAS cells, and we identified miR-629-3p as being responsible for acquiring anticancer drug resistance in head and neck cancer. The introduction of miR-629-3p expression inhibited apoptotic cell death under cisplatin treatment conditions, and it promoted cell migration. Among the computationally predicted target genes of miR-629-3p, we found that a number of gene expressions were suppressed by the transfection with miR-629-3p. Using a xenografting model, we showed that miR-629-3p conferred cisplatin resistance to SAS cells. Clinically, increased miR-629-3p expression tended to be associated with decreased survival in head and neck cancer patients. In conclusion, our data suggest that the increased expression of miR-629-3p provides a mechanism of cisplatin resistance in head and neck cancer and may serve as a therapeutic target to reverse chemotherapy resistance.

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EZH2 contributes to 5-FU resistance in gastric cancer by epigenetically suppressing FBXO32 expression

Cited by 35 publications

References 24 publications

UNC5B‐AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2

UNC5B‐AS1 promoted ovarian cancer progression by regulating the H3K27me on NDRG2 via EZH2

Involvement of ribosomal protein L11 expression in sensitivity of gastric cancer against 5‑FU

CD44s Induces miR-629-3p Expression in Association with Cisplatin Resistance in Head and Neck Cancer Cells

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