Association of AlkB homolog 3 expression with tumor recurrence and unfavorable prognosis in hepatocellular carcinoma

Wang, Qian; Wang, Gang; Wang, Yi; Liu, Chaoxu; He, Xianli

doi:10.1111/jgh.14117

Cited by 20 publications

(14 citation statements)

References 26 publications

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“…Western blot and immunohistochemistry staining were performed as previously described ( 19 ). For western blot assay, the primary antibodies against DUSP9 (1:2000, Abcam, cat.…”

Section: Methodsmentioning

confidence: 99%

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Downregulation of DUSP9 Promotes Tumor Progression and Contributes to Poor Prognosis in Human Colorectal Cancer

Qiu

Liang

Huang³

et al. 2020

Front. Oncol.

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Background: Dual-specificity phosphatase 9 (DUSP9) belongs to the dual-specificity protein phosphatase subfamily. Recently, increasing attention has been paid on the role of DUSP9 in a variety of cancers. However, its functional role in tumor development is still unclear, especially in colorectal cancer (CRC). Methods: The functional role of DUSP9 in inhibiting the progression of CRC was verified using colony formation assay, wound healing assay, nude mice xenograft model, etc. RNA-seq was performed to assess the gene expression profiling in SW480 cells with DUSP9 stable knockdown and shControl cells. Bisulfite sequencing (BSE) was performed to reveal the methylation status of CpG island in the promoter of DUSP9. Results: DUSP9 was significantly downregulated in tumor tissues compared with peritumor tissues. Mechanistically, the high methylation status of CpG island in the promoter of DUSP9 may lead to the downregulation of DUSP9 in CRC. Clinically, low DUSP9 expression in CRC was closely associated with depth of invasion, metastasis (TNM) stage, and poor survival, indicating that DUSP9 may be involved in the progression of CRC. Functional study revealed that DUSP9 inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition of CRC cells both in vitro and in vivo. Transcriptome profiling studies revealed that Erk signaling was involved in the tumor progression mediated by DUSP9 silencing, which is confirmed by cell experiments and clinical tissue sample staining analysis. Conclusion: Our findings demonstrate that DUSP9 plays a critical role in the progression of CRC, and therapeutic intervention to increase the expression or activity of DUSP9 may be a potential target for CRC treatment in the future.

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“…Western blot and immunohistochemistry staining were performed as previously described ( 19 ). For western blot assay, the primary antibodies against DUSP9 (1:2000, Abcam, cat.…”

Section: Methodsmentioning

confidence: 99%

“…179467) were used in accordance with the manufacturer’s instructions. Signals were detected using an ECL kit (Pierce, Rockford, IL) as previously reported ( 19 ). For immunohistochemistry staining, primary antibodies against DUSP9 (1:200, Abcam, cat.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of DUSP9 Promotes Tumor Progression and Contributes to Poor Prognosis in Human Colorectal Cancer

Qiu

Liang

Huang³

et al. 2020

Front. Oncol.

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“…ALKBH4 belongs to the AlkB family of non-heme Fe (II)/a-ketoglutarate-dependent dioxygenases, whose function have been implicated in the repair of methylation damage in DNA and RNA (Lee et al, 2005). Available evidences also indicate that several members of AlkB family, such as ALKBH3 and ALKBH5, are closely linked to the inhibition of tumorigenesis and progression in various human cancers (Stefansson et al, 2017;Wang et al, 2018;Zhu et al, 2019). ALKBH4 has been previously illustrated in mediating demethylation of a monomethylated site in actin and depletion of ALKBH4 contributes to defects in cytokinesis and cell motility (Li et al, 2013), however, the underlying molecular mechanisms of ALKBH4 in tumor remain unknown.…”

Section: Discussionmentioning

confidence: 99%

ALKBH4 Functions as a Suppressor of Colorectal Cancer Metastasis via Competitively Binding to WDR5

Shen

Yan

Tong

et al. 2020

Front. Cell Dev. Biol.

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Background: Epithelial-Mesenchymal Transition (EMT) is a major process in the initiation of tumor metastasis, where cancer cells lose sessile epithelial potential and gain mesenchymal phenotype. Large-scale cell identity shifts are often orchestrated on an epigenetic level and the interplay between epigenetic factors and EMT progression was still largely unknown. In this study, we tried to identify candidate epigenetic factors that involved in EMT progression. Methods: Colorectal cancer (CRC) cells were transfected with an arrayed shRNA library targeting 384 genes involved in epigenetic modification. Candidate genes were identified by real-time PCR. Western blot, RNA-seq and gene set enrichment analysis were conducted to confirm the suppressive role of ALKBH4 in EMT. The clinical relevance of ALKBH4 in CRC was investigated in two independent Renji Cohorts and a microarray dataset (GSE21510) from GEO database. In vitro transwell assay and in vivo metastatic tumor model were performed to explore the biological function of ALKBH4 in the metastasis of CRC. Co-IP (Co-Immunoprecipitation) and ChIP (Chromatin Immunoprecipitation) assays were employed to uncover the mechanism. Results: We screened for candidate epigenetic factors that affected EMT process and identified ALKBH4 as a candidate EMT suppressor gene, which was significantly downregulated in CRC patients. Decreased level of ALKBH4 was associated with metastasis and predicted poor prognosis of CRC patients. Follow-up functional experiments illustrated overexpression of ALKBH4 inhibited the invasion ability of CRC cells in vitro, as well as their metastatic capability in vivo. Mechanistically, CO-IP and ChIP assays indicated that ALKBH4 competitively bound WDR5 (a key component of

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“…Moreover, recent research has identified another m 6 A demethylase, ALKBH3 (43). Wang et al (86) reported that ALKBH3 was overexpressed in HCC and high ALKBH3 expression in HCC tissues decreased OS and disease-free survival in HCC patients. ALKBH3 knockdown inhibited human HCC cell proliferation in vitro and xenograft tumor formation in vivo, presumably through p21/p27-mediated cell cycle arrest at the G1 phase (86).…”

Section: Erasers and Hccmentioning

confidence: 99%

Role of N6-Methyladenosine (m6A) Methylation Regulators in Hepatocellular Carcinoma

et al. 2021

Front. Oncol.

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Liver cancer is the fifth most common malignant tumor in terms of incidence and the third leading cause of cancer-related mortality globally. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Although great progress has been made in surgical techniques, hepatic artery chemoembolization, molecular targeting and immunotherapy, the prognosis of liver cancer patients remains very poor. N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells and regulates various stages of the RNA life cycle. Many studies have reported that the abnormal expression of m6A-related regulators in HCC represent diagnostic and prognostic markers and potential therapeutic targets. In this review, firstly, we introduce the latest research on m6A-related regulators in detail. Next, we summarize the mechanism of each regulator in the pathogenesis and progression of HCC. Finally, we summarize the potential diagnostic, prognostic and therapeutic value of the regulators currently reported in HCC.

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Association of AlkB homolog 3 expression with tumor recurrence and unfavorable prognosis in hepatocellular carcinoma

Abstract: These findings reveal an important role of ALKBH3 in HCC, indicating that ALKBH3 could be used as a new therapeutic target in future.

Cited by 20 publications

References 26 publications

Downregulation of DUSP9 Promotes Tumor Progression and Contributes to Poor Prognosis in Human Colorectal Cancer

Downregulation of DUSP9 Promotes Tumor Progression and Contributes to Poor Prognosis in Human Colorectal Cancer

ALKBH4 Functions as a Suppressor of Colorectal Cancer Metastasis via Competitively Binding to WDR5

Role of N6-Methyladenosine (m6A) Methylation Regulators in Hepatocellular Carcinoma

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