shRNA knockdown of DNA helicase ERCC6L expression inhibits human breast cancer growth

Liu, Juan; Sun, Jing; Zhang, Qian; Zeng, Zhao‐Chong

doi:10.3892/mmr.2018.9317

Cited by 14 publications

(13 citation statements)

References 23 publications

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“…ERCC6L deletion in mammalian cells can lead to cell cycle arrest, DNA damage, chromosomal abnormities, TP53 activation and apoptosis (8,33). Importantly, upregulation of ERCC6L has been identified in several cancers and is related to cancer progression and poorer prognosis of patients (5,7,(9)(10)(11). Huang et al found that ERCC6L was indispensable for the chromosome stability of cancer cells, and silencing ERCC6L could lead to apoptosis induction and proliferation inhibition of triple-negative breast cancer cells in vivo and in vitro by inducing the formation of chromatin bridges and mitotic catastrophe (7).…”

Section: Discussionmentioning

confidence: 99%

“…For example, Pu et al demonstrated that overexpression of ERCC6L in breast and kidney cancers correlated with the progression of disease and poorer survival of cancer patients (9). Huang et al showed that silencing ERCC6L in cancer cells (such as liver, breast, colorectal and kidney cancers) resulted in cell cycle arrest, proliferation inhibition, invasion reduction and apoptosis (5,7,(10)(11)(12). The above studies undoubtedly indicate the key implications of ERCC6L dysregulation in tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of ERCC6L is associated with tumor progression and unfavorable prognosis in hepatocellular carcinoma

Liang

et al. 2020

J Gastrointest Oncol

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Background: The oncogenic role of excision repair cross-complementation group 6-like (ERCC6L) has been revealed in several cancers recently, but little is known about its expression and function in hepatocellular carcinoma (HCC).Methods: Utilizing public data from Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA) databases, ERCC6L dysregulation in HCC and its clinical significance were determined by t-test and Chisquare test. Comprehensive survival analyses (such as nomogram, Cox regression model and Kaplan-Meier analysis) were performed to assess prognostic value of ERCC6L for HCC patients. Integrated bioinformatics analyses [including copy number alterations (CNA), DNA methylation, miRNA prediction and gene set enrichment analysis (GSEA)] were conducted to explore the mechanisms and biological roles underlying ERCC6L dysregulation in HCC.Results: ERCC6L upregulation was identified in HCC tissues compared to normal controls (P<0.05). In addition, overexpression of ERCC6L not only correlated with elevated alpha fetoprotein (AFP), vascular invasion (VI), and advanced histologic grade and TNM stage, but also had an independent prognostic value for the poorer overall survival (OS) and recurrence-free survival (RFS) of HCC patients (all P<0.05). Besides, nomogram integrating ERCC6L expression and TNM stage showed superior prognostic ability than that of TNM stage (P<0.05). Moreover, ERCC6L promoter hypomethylation and miR-5589 downregulation in HCC might result in ERCC6L overexpression (all P<0.05). Furthermore, eight biological pathways (including the DNA replication, cell cycle and p53 pathways) related to ERCC6L upregulation in HCC were found to be enriched by GSEA, and ERCC6L upregulation was positively correlated with PLK1 (polo-like kinase 1) expression and TP53 mutation in HCC, which preliminarily shed light on the roles of ERCC6L in HCC.Conclusions: ERCC6L may serve as a promising prognostic indicator and therapeutic target for HCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upregulation of ERCC6L is associated with tumor progression and unfavorable prognosis in hepatocellular carcinoma

Liang

et al. 2020

J Gastrointest Oncol

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“…Excision repair cross-complementation group 6-like (ERCC6L), also named as Polo-like kinase 1-interacting checkpoint “helicase” (PICH), which was identified as an embryonic development related proteins, has been shown to play critical roles in regulating the development of embryonic, brain and other tissues [ 6 – 8 ]. Recently several reports revealed that abnormal ERCC6L expression has been detected in several malignant solid tumors consisting of breast cancer [ 9 ], kidney cancer [ 10 ], and neuroblastoma [ 11 ]. In addition, high ERCC6L expression level is related to poor prognosis in breast cancer patients, and may regulate cell proliferation, invasion and metastasis by regulating different single pathways.…”

Section: Introductionmentioning

confidence: 99%

ERCC6L promotes the progression of hepatocellular carcinoma through activating PI3K/AKT and NF-κB signaling pathway

Han

Wang

et al. 2020

BMC Cancer

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Background: Excision Repair Cross-Complementation group 6-like (ERCC6L) has been shown to exhibit carcinogenic effect in several malignant tumors. However, the function and molecular mechanism of the ERCC6L in hepatocellular carcinoma (HCC) have not been investigated extensively. Methods: Immunohistochemistry analyses were used to detect ERCC6L expression in a HCC tissue microarray, and the Chi-square test was used to assess the correlation between ERCC6L expression and patients' clinicopathological features. shRNA was used to down-regulation ERCC6L expression in HCC cell lines. MTT assay, plate clone formation assay, flow cytometry, caspase 3/7 activity and migration assays were performed to evaluate the impact of ERCC6L on HCC cells in vitro. Nude mice xenograft models were used to assess the role of ERCC6L in vivo. The regulatory of mechanism of PI3K/AKT pathway was evaluated by western blotting. Results: ERCC6L was highly expressed in HCC tissue compared with tumor adjacent tissues in 90 paired samples. ERCC6L expression positively correlated with gender, tumor encapsulation, and pathological stage. Patients with low ERCC6L expression had significantly longer OS than those with high ERCC6L expression. Knockdown of ERCC6L expression significantly inhibited proliferation, invasion and metastasis in vitro and tumor growth in vivo, and it promoted cell cycle arrest and apoptosis. Mechanistic analyses revealed that PI3K/AKT and NF-κB signaling pathway were inhibited by silencing ERCC6L. Conclusion: These results demonstrate that ERCC6L plays a critical role in HCC progression, and thereby might be a potential therapeutic target for HCC patients.

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“…VNTR 945060 is in the 5’UTR of ERCC6L , a DNA helicase. ERCC6L is highly expressed in breast tissue and higher levels of expression have been associated with worse survival [33]; silencing of ERCC6L in breast cell lines significantly inhibited cell proliferation [33, 34]. A second VNTR, 253688, is located 3’ of FLJ22447 , a lncRNA located near HIF-1α .…”

Section: Discussionmentioning

confidence: 99%

Variable Number Tandem Repeats (VNTRs) as modifiers of breast cancer risk in carriers of BRCA1 185delAG

Ding

Adamson

Bakhtiari

et al. 2022

Preprint

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Despite substantial efforts in identifying both rare and common variants affecting disease risk, in the majority of diseases, a large proportion of unexplained genetic risk remains. We propose that variable number tandem repeats (VNTRs) may explain a proportion of the missing genetic risk. Herein, we tested whether VNTRs are causal modifiers of breast cancer risk in 347 female carriers of BRCA1 185delAG, an important group given their high risk of developing breast cancer. We performed targeted-capture to sequence VNTRs, called genotypes with adVNTR, and tested the association of VNTRs and breast cancer risk using Cox regression models. Of 303 VNTRs that passed quality control checks, 4 VNTRs were significantly associated with risk to develop breast cancer at false discovery rate [FDR] < 0.05 and an additional 4 VNTRs had FDR < 0.25. After determining the specific risk alleles, there was a significantly earlier age at development of breast cancer in carriers of the risk genotypes compared to those without the risk genotypes for seven of eight VNTRs. Results from this first systematic study of VNTRs demonstrate that VNTRs may explain a proportion of the unexplained genetic risk for disease and have larger effects than SNPs.

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shRNA knockdown of DNA helicase ERCC6L expression inhibits human breast cancer growth

Cited by 14 publications

References 23 publications

Upregulation of ERCC6L is associated with tumor progression and unfavorable prognosis in hepatocellular carcinoma

Upregulation of ERCC6L is associated with tumor progression and unfavorable prognosis in hepatocellular carcinoma

ERCC6L promotes the progression of hepatocellular carcinoma through activating PI3K/AKT and NF-κB signaling pathway

Variable Number Tandem Repeats (VNTRs) as modifiers of breast cancer risk in carriers of BRCA1 185delAG

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