The histone demethylase lysine-specific demethylase-1–mediated epigenetic silence of KLF2 contributes to gastric cancer cell proliferation, migration, and invasion

Fang, Ruizhong; Xu, Jian; Lin, Hai; Xu, Xiaoguang; Tian, Feng

doi:10.1177/1010428317698356

Cited by 10 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that KDM1A promoted cancer progression by removing methyl groups from the methylated histones H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) ( 37 ). KDM1A was overexpressed in various malignant tumors, including cervical cancer ( 38 ), esophageal cancer ( 39 ), ovarian cancer ( 40 ), and GC ( 41 ). The elevated KDM1A level was also related to tumor stage, histological grade, and lymph node metastasis ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: OTUB2 Facilitates Tumorigenesis of Gastric Cancer Through Promoting KDM1A-Mediated Stem Cell-Like Properties

2021

View full text Add to dashboard Cite

Otubain 2 (OTUB2), a deubiquitinating enzyme, overexpression is considered to predict poor outcome in various cancers. However, the function and potential regulatory mechanisms of OTUB2 in gastric cancer (GC) progression remains unclear. To determine how OTUB2 participate in GC progression, the gain and loss of-function experiments were conducted in vivo and in vitro. We found that OTUB2 was upregulated in GC samples (n=140) and cells. Moreover, the overall, first progression and post progression survival rates of GC patients with high OTUB2 expression showed a poorer prognosis than that in those patients with low OTUB2 expression. Down-regulation of OTUB2 suppressed sphere formation and reduced expression of stem cell markers in GC cells. Furthermore, OTUB2-silenced GC cells also showed a decreased proliferation, invasion, migration, and in vivo tumorigenic ability. However, OTUB2 overexpression showed the opposite effects. Notably, we demonstrated that OTUB2 increased lysine-specific histone demethylase 1A (KDM1A) expression through deubiquitination. KDM1A, a demethylase known to promote demethylation of downstream genes, was identified to promote the maintenance of cancer stem cell characteristics. Moreover, the alterations caused by OTUB2 overexpression were partly inversed by KDM1A knockdown and in turn KDM1A overexpression reversed the changes induced by OTUB2 shRNA. Taken together, we demonstrate that OTUB2 may serve as a vital driver in GC tumorigenesis by enhancing KDM1A-mediated stem cell-like properties.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED: OTUB2 Facilitates Tumorigenesis of Gastric Cancer Through Promoting KDM1A-Mediated Stem Cell-Like Properties

2021

View full text Add to dashboard Cite

show abstract

“…For example, the lncRNA HOXA11‐AS Promotes Proliferation and Invasion of Gastric Cancer by Scaffolding the Chromatin Modification Factors PRC2, LSD1, and DNMT1 (Sun, Nie, et al, ); lincRNAFEZF1‐AS1 represses p21 expression to promote gastric cancer proliferation through LSD1‐Mediated H3K4me2 demethylation (Liu, Xia, et al, ); and lncRNA 00511 Acts as an Oncogene in Non‐small‐cell Lung Cancer by Binding to EZH2 and Suppressing p57 (Sun, Li, et al, ). KLF2, a tumor suppressor and the member of KLF family with Cys2/His2 zinc‐finger domains, is dysregulated in multiple cancers (Dimmeler et al, ; Fang, Xu, Lin, Xu, & Tian, ; Manavski et al, ). It has been demonstrated that EZH2 could directly bind to KLF2 promoter and silence of KLF2 expression result in the blocking of tumor suppressor features of KLF2 (Huang et al, ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA GHET1 predicts poor prognosis in hepatocellular carcinoma and promotes cell proliferation by silencing KLF2

Jin

Tang

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) has been identified as one of the leading causes of cancer-related death worldwide. Recently, long non-coding RNAs (lncRNAs) attract much attention of researchers, and they are demonstrated to be dysregulated in a variety of cancers, including HCC. LncRNA gastric carcinoma high expressed transcript 1 lncRNA GHET1 is found to be dysregulated in gastric cancer (GC). However, its clinical value and potential biological function in HCC remains unclear. In this study, the expression level of GHET1 was analyzed in 72 HCC tissues and matched normal tissues by using Quantitative RT-PCR (qRT-PCR). GHET1 expression was significantly up-regulated in HCC tissues and the higher level of GHET1 was related to vascular invasion, cirrhosis, tumor size, edmindson grade, and poor prognosis. Moreover, knockdown of GHET1 inhibited cell proliferation of HCC, and also caused cell cycle arrest and induced apoptosis in HCC cell lines. We also found that GHET1 could epigenetically repress transcription of Kruppel-like factor 2 (KLF2) in HCC cells by recruiting PRC2 into KLF2 promoter region. Our results indicated that lncRNA GHET1, as a growth regulator, might serve as a novel prognostic biomarker and therapy target for HCC.

show abstract

“…Kruppel‐like factor 2 (KLF2), a tumor suppressor, is dysregulated in various cancers . Ma et al revealed that KLF2 was downregulated by LncRNA SNHG15 to promote pancreatic cancer proliferation .…”

Section: Discussionmentioning

confidence: 99%

Knockdown of LncRNA GHET1 suppresses prostate cancer cell proliferation by inhibiting HIF‐1α/Notch‐1 signaling pathway via KLF2

Zhu

Tong

Wu³

et al. 2019

BioFactors

View full text Add to dashboard Cite

Prostate cancer (PC) is one of the most common cancers in male groups worldwide. Long noncoding RNAs (LncRNAs) are reported to be dysregulated in a variety of cancers, including PC. This study aimed to explore the role of LncRNA GHET1 in the pathogenesis of PC. RT-qPCR was carried out to examine the relative expression level of GHET1 in PC patients. In vitro, GHET1 siRNA (si-GHET1) was used to investigate the biological role of GHET1 in PC cell lines. Cell proliferation was detected by CCK-8 and colony formation assay, while cell cycle and cell apoptosis were analyzed using flow cytometry. Moreover, western blot was carried out to measure the protein expression levels of KLF2 and HIF-1α/Notch-1 signal pathway. We found that GHET1 showed higher expression in PC tissues and had a negative correlation with KLF2 expression. Knockdown of GHET1 significantly suppressed the cell proliferation, induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis. Additionally, si-GHET1 transfection induced KLF2 upregulation and HIF-1α/Notch-1 signal pathway suppression, which could be rescued by si-KLF2 transfection. These results suggest the key role of GHET1 in PC progression. Moreover, GHET1 might be explored to be a potential target for clinical treatment of PC.

show abstract

The histone demethylase lysine-specific demethylase-1–mediated epigenetic silence of KLF2 contributes to gastric cancer cell proliferation, migration, and invasion

Cited by 10 publications

References 34 publications

RETRACTED: OTUB2 Facilitates Tumorigenesis of Gastric Cancer Through Promoting KDM1A-Mediated Stem Cell-Like Properties

RETRACTED: OTUB2 Facilitates Tumorigenesis of Gastric Cancer Through Promoting KDM1A-Mediated Stem Cell-Like Properties

LncRNA GHET1 predicts poor prognosis in hepatocellular carcinoma and promotes cell proliferation by silencing KLF2

Knockdown of LncRNA GHET1 suppresses prostate cancer cell proliferation by inhibiting HIF‐1α/Notch‐1 signaling pathway via KLF2

Contact Info

Product

Resources

About