The developmental transcription factor IRF6 attenuates ABCG2 gene expression and distinctively reverses stemness phenotype in nasopharyngeal carcinoma

Xu, Liang; Huang, Tie Jun; Hu, Hao; Wang, Meng Yao; Shi, Si; Qin, Yang; Lin, Feifei; Qiang, Yuan Yuan; Yan, Mei; Ling, Yan; Li, Chang‐Zhi; Li, Peng; Zheng, Lichun; Huang, Junting; Li, Xin Jian; Zhang, Shi Jun; Qian, Chao Nan; Huang, Bi

doi:10.1016/j.canlet.2017.10.016

Cited by 39 publications

(29 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 Emerging evidence has demonstrated a downregulation of IRF6 in several malignant tumors, including breast cancer, squamous cell carcinomas and nasopharyngeal carcinoma. 15,30,31 A detailed study demonstrated that overexpression of IRF6 led to breast cancer MDA-MB-231 growth suppression in vivo and in vitro and enhanced dose-dependent sensitivity to cisplatin. 15 IRF6 expression was shown to be significantly decreased in gastric cancer, and gastric cancer patients with lower expression of IRF6 are predicted to have a shorter overall survival time and disease-free time.…”

Section: Discussionmentioning

confidence: 99%

miR‐587 promotes cervical cancer by repressing interferon regulatory factor 6

Ren

Dong

et al. 2020

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background: Interferon regulatory factor 6 (IRF6) exhibits tumor-suppressive functions in several cancer types. In the present study, the antitumor properties and related pathway mechanism of IRF6 were investigated in cervical cancer. Methods: Forty-one pairs of cervical cancer specimens and para-carcinoma tissues were collected to evaluate IRF6 expression using immunohistochemical staining and miR-587. The effects of miR-587 and IRF6 on cervical cancer cell growth were explored by MTT assays and in a HeLa tumor xenograft mouse model. The migration and invasion of cervical cancer cells were monitored using transwell assays. Results: IRF6 expression in cervical cancer specimens and cell lines was significantly reduced compared to that in the corresponding control group. In addition, IRF6 expression was negatively correlated with miR-587 in cervical cancer tissues. Bioinformatics algorithms and luciferase assays revealed that IRF6 is a potential target of miR-587, and miR-587 mimic transfection led to a significant repression of IRF6 protein levels in cervical cancer cells. We also discovered that the antineoplastic properties of IRF6 could be reversed by overexpressing miR-587 in cervical cancer cells. The up-regulation of miR-587 was correlated with poor overall survival in cervical cancer. In an in vivo experiment, miR-587 silencing induced HeLa tumor growth inhibition, which was associated with the up-regulation of IRF6 protein in the tumor. Conclusions: miR-587 post-transcriptionally represses IRF6 protein expression to abrogate the antineoplastic activity of IRF6. The miR-587/IRF6 signaling pathway plays a crucial role in the progression of cervical cancer and serves as a potential therapeutic target for the treatment of cervical cancer. K E Y W O R D S cervical cancer, interferon regulatory factor 6, miR-587, prognosis 1 | INTRODUCTION Cervical cancer is one of the most common gynecologic malignant neoplasms and ranks fourth for both incidence and mortality in females. 1 According to an epidemiological investigation, cervical cancer accounted for approximately 6.6% of the total incidents and 7.5% of the total cancer deaths among females in 2018. 1 In general, persistent human papillomavirus infection can lead to intraepithelial lesions of the cervix uteri, which is an inevitable cancerous process of cervical cancer. 2,3 The mechanisms of cervical carcinogenesis are complicated. Different signaling pathways, such as nuclear factorkappa B, mammalian target of rapamycin, phosphoinositide 3-kinase Yuefang Ren and Jie Dong contributed equally to this work.

show abstract

Section: Discussionmentioning

confidence: 99%

miR‐587 promotes cervical cancer by repressing interferon regulatory factor 6

Ren

Dong

et al. 2020

The Journal of Gene Medicine

View full text Add to dashboard Cite

show abstract

“…Specific markers are present in stem cells. For example, there are several biomarkers for CSCs, including SOX2, Bmi1, CD44, Nanog, and ABCG2 [27,28]. CD133 is a specific CSC marker in HCC.…”

Section: Discussionmentioning

confidence: 99%

Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal

Luo

Cao

et al. 2020

J. Cancer

Self Cite

View full text Add to dashboard Cite

Depressive disorder (DD) is the leading cause of disability worldwide and is the most prevalent mood disorder. Accumulative evidence from epidemiological studies has shown that DD is a risk factor for cancer. However, the role and molecular mechanism of DD in hepatocellular carcinoma (HCC) are still unknown. In this study, 30 mice were randomly divided into two groups: the HCC group and the HCC-DD group. The DD mouse model of HCC was established by induction with reserpine every other day and with monthly doses of diethylnitrosamine (DEN). All of the molecular studies were based on primary cell culture, and the effects of DD on HCC cell proliferation and migration and cancer stem cell (CSC) self-renewal were determined by colony formation, wound healing, and sphere culture assays. We found that the CSC markers ABCG2 and CD133 were upregulated in HCC-DD primary cells compared with HCC primary cells. Moreover, HCC-DD primary cells were more aggressive in terms of metastasis and self-renewal than HCC primary cells. Further study revealed that DD promoted tumor growth and metastasis by activating the AKT signaling pathway followed by an increased ABCG2 expression. Taken together, our novel findings indicate that DD promotes proliferation, self-renewal, and metastasis by upregulating ABCG2 in the AKT pathway.

show abstract

“…e expression of ABCC1 and ABCG2 in NPC tissues is significantly higher than that in normal nasopharyngeal tissues by real-time PCR [32]. ABCB1 gene polymorphism and ABCG2 upregulation may be responsible for the resistance of NPC cancer stem cells to chemotherapeutic drugs [33,34]; tumour suppressor gene IRF6 kills cancer stem cells in NPC by targeting the ABCG2 gene [35].…”

Section: Discussionmentioning

confidence: 99%

Study on the Drug Targets and Molecular Mechanisms of Rhizoma Curcumae in the Treatment of Nasopharyngeal Carcinoma Based on Network Pharmacology

Zhai

Huang

Liao

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Aim. To analyse the target of Rhizoma Curcumae in nasopharyngeal carcinoma by using network pharmacological techniques and to explore the associated molecular mechanism. Methods. The targets of nasopharyngeal carcinoma were retrieved from the GeneCards database. At the same time, the drug therapeutic targets of Rhizoma Curcumae were obtained from the TCMSP and SymMap databases. The data were imported into the STRING database and Cytoscape 3.7.1 to construct a network of “Chinese medicine component-target-disease” interactions; then, the intersection was screened as the core Rhizoma Curcumae antinasopharyngeal cancer targets. Through GO target function and KEGG pathway enrichment analyses of the core targets, we predicted the biological processes and key signalling pathways involved in the Rhizoma Curcumae treatment of nasopharyngeal carcinoma. Results. Twenty-five core targets of Rhizoma Curcumae in nasopharyngeal carcinoma were mined: TP53, BCL2 ICAM1 RXRA, TLR3 and TLR9, TNF, PTGS2, IL-6, CTSD, MMP2, MMP9, MMP14, TIMP2, ABCC1, ABCB1, ABCG2, and so on. The results of visual analysis showed that the Rhizoma Curcumae treatment of nasopharyngeal carcinoma mainly involves leukocyte adhesion to vascular endothelial cells, positive regulation of NF-κB import into the nucleus, regulation of the reactive oxygen species biosynthetic and metabolic process, regulation of the chemokine biosynthetic and metabolic process, various cancer-related signalling pathways, and a variety of cytokine signal transduction pathways, such as the NF-κB, TLR, IL-17, and TNF signalling pathways. Conclusion. The core targets predicted by our research can be used as molecular markers for the treatment and prediction of nasopharyngeal carcinoma. The mechanism of Rhizoma Curcumae treatment in NPC may be related to immune regulatory pathways, the inhibition of cancer cell proliferation, metastasis, and angiogenesis, as well as the regulation of tumour microenvironment. Combined with the prediction of its associated mechanism of action, the core targets can provide targeted reference value for subsequent drug development related to Curcuma.

show abstract

The developmental transcription factor IRF6 attenuates ABCG2 gene expression and distinctively reverses stemness phenotype in nasopharyngeal carcinoma

Cited by 39 publications

References 43 publications

miR‐587 promotes cervical cancer by repressing interferon regulatory factor 6

miR‐587 promotes cervical cancer by repressing interferon regulatory factor 6

Depressive Disorder promotes Hepatocellular Carcinoma metastasis via upregulation of ABCG2 gene expression and maintenance of self-renewal

Study on the Drug Targets and Molecular Mechanisms of Rhizoma Curcumae in the Treatment of Nasopharyngeal Carcinoma Based on Network Pharmacology

Contact Info

Product

Resources

About