Epigenetic activation of FOXF1 confers cancer stem cell properties to cisplatin‑resistant non‑small cell lung cancer

Zhao, Jian; Xue, Xingyang; Fu, Wanyi; Dai, Lu; Jiang, Zeyong; Zhong, Shengpeng; Deng, Boyun; Yin, Jun

doi:10.3892/ijo.2020.5003

Cited by 11 publications

(9 citation statements)

References 40 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Foxf1 is a member of the forkhead box family of transcription factor and has been previous reported to be critical for multiple human cancer, such as colorectal cancer [27], gastrointestinal stromal tumor [28] breast cancer [29,30] and non-small cell lung cancer [31]. we found that the downregulation of Foxf1 was signi cantly correlated with a poorer prognosis for patients with prostate cancer.…”

Section: Discussionmentioning

confidence: 49%

Emerging biomarker associated with prognosis of prostate cancer identified via co-expression analysis

Liang

Chen

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Forkhead box protein f1 (Foxf1) is associated with oncogenesis, and maybe play a key role in prostate cancer. However, the effect of Foxf1 on the development of prostate cancer and its clinical implications were still unknown. Method: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The differential co-expression genes which were the most closely correlated with prostate cancer were identified by weighted gene co-expression network analysis (WGCNA) and differential expression analysis method. The univariate cox regressions were performed to identify the prognostic genes. Finally, Foxf1 were verified in clinical tumor samples and matched normal tissues. Results: A total of 108 differential co-expression genes were identified. Foxf1 was identified that significantly associated with overall survival rate and biochemical recurrence of prostate. Then, protein-protein interaction (PPI) networks were constructed, including 21 nodes and 26 edges. The data revealed GAPVD1, MIR522, MIR937, CPS1, HOXB9, FUBP3, MIR936, SDF4, SATB2, HOXB13, MIR375, PUSL1, SATB1, MIR382, MIR429, HOXD13, PRSS50, FLNC, STRBP, KHSRP were significant associated with the regulation and function of differentially expressed Foxf1 in prostate. The experimental results confirmed the Foxf1 were downregulated in the prostate cancer tissues compared with the matched normal tissues.Conclusion: we obtained a gene Foxf1 which is significantly related with the prognosis of prostate cancer, Foxf1 have significant values in predicting the patients’ Overall survival and may serve as a potential prognosis biomarker and a new therapeutic target of prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 49%

Emerging biomarker associated with prognosis of prostate cancer identified via co-expression analysis

Liang

Chen

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…DNA hypermethylation of the CLDN1 promoter represses lung cancer stem cell-like phenotype and enhances chemotherapeutic efficacy [ 39 ]. However, hypomethylation of FOXF1 facilitates cell proliferation, acquires cancer stem properties, and inhibited cell apoptosis to induce cisplatin resistance in NSCLC [ 36 ]. Here, we demonstrated DNMT3A-mediated SFRP1 methylation promoted tumor progression in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…Since epigenetic alterations have been found to contribute the programing of the stem cells that causes normal stem cells to CSCs with loss of the multilineage differentiation potential and maintain the stem-like properties such as selfrenew, proliferation, and invasion of distal tumor sites [33]. Epigenic modification such as DNA methylation and histone methylation reprogram CSCs contributes to multiple cancer initiation, progression, and therapy responses [34][35][36]. DNA methylation is a pivotal mechanism in cancer that regulate gene expression and cell fate commitment [37,38].…”

Section: Discussionmentioning

confidence: 99%

miR-26a-5p Suppresses Wnt/β-Catenin Signaling Pathway by Inhibiting DNMT3A-Mediated SFRP1 Methylation and Inhibits Cancer Stem Cell-Like Properties of NSCLC

Yu¹,

Chen

et al. 2022

Disease Markers

View full text Add to dashboard Cite

Background. Lung cancer is a malignant cancer which results in the most cancer incidence and mortality worldwide. There is increasing evidence that the pattern of DNA methylation affects tumorigenesis and progression. However, the molecules and mechanisms regulating DNA methylation remain unclear. Methods. The expression of miR-26a-5p in NSCLC cell lines was detected by qPCR and verified in NSCLC tissues from TCGA using Limma R package. CCK-8 assay, plate clone formation assay, flow cytometry, and sphere formation assay were used to detect the cell proliferation, colony formation, cell cycle, and cancer stem cell- (CSC-) like property in NSCLC cell lines. The immunoblotting was used to detect the protein levels of DNMT3A, SFRP1, and Ki67. Global DNA methylation levels and DNA methylation levels of SFRP1 promoter were examined using ELISA and MSP-PCR assay, respectively. The distribution of β-catenin was examined using immunofluorescence (IF). Besides, xenograft mouse model was used to investigate the antitumor effects of miR-26a-5p in vivo. The pathology and protein levels were, respectively, detected by hematoxylin and eosin (H&E) and immunocytochemistry (IHC). Results. The expression of miR-26a-5p was downregulated in the tumor tissues comparted to adjacent normal tissues as well as NSCLC cell lines compared to normal lung epithelial cell (BEAS2B). The overexpression of miR-26a-5p inhibited cell proliferation, colony formation, CSC-like property, and arrested cell cycle at G1 phase. DNMT3A was a target of miR-26a-5p and upregulated DNA methylation on SFRP1 promoter. Mechanistically, miR-26a-5p repressed cell proliferation, colony formation, CSC-like property, and arrested cell cycle at G1 phase by binding DNMT3A to reduce DNA methylation levels of SFRP1 then upregulated SFRP1 expression. Moreover, miR-26a-5p exerted antitumor effects in vivo. Conclusion. Our results revealed that miR-26a-5p acted as a tumor suppressor through targeting DNMT3A to upregulate SFRP1 via reducing DNMT3A-dependent DNA methylation.

show abstract

“…Although cisplatin or cis-diamminedichloroplatinum (II) has been widely used as a first-line platinum based-chemotherapy for lung cancer patients [ 71 ], eventual drug resistance and cancer relapse severely limit clinical benefit [ 72 , 73 ]. The subpopulation of CSCs in tumors are recognized contributors to cisplatin resistance in lung cancer [ 23 , 74 , 75 ]. The promising CSC-targeting activity of jorunnamycin A was demonstrated by its enhancement of cisplatin-induced apoptosis in CSC-enriched spheroids ( Figure 8 C,D).…”

Section: Discussionmentioning

confidence: 99%

Jorunnamycin A Suppresses Stem-Like Phenotypes and Sensitizes Cisplatin-Induced Apoptosis in Cancer Stem-Like Cell-Enriched Spheroids of Human Lung Cancer Cells

et al. 2021

View full text Add to dashboard Cite

It has been recognized that cancer stem-like cells (CSCs) in tumor tissue crucially contribute to therapeutic failure, resulting in a high mortality rate in lung cancer patients. Due to their stem-like features of self-renewal and tumor formation, CSCs can lead to drug resistance and tumor recurrence. Herein, the suppressive effect of jorunnamycin A, a bistetrahydroisoquinolinequinone isolated from Thai blue sponge Xestospongia sp., on cancer spheroid initiation and self-renewal in the CSCs of human lung cancer cells is revealed. The depletion of stemness transcription factors, including Nanog, Oct-4, and Sox2 in the lung CSC-enriched population treated with jorunnamycin A (0.5 μM), resulted from the activation of GSK-3β and the consequent downregulation of β-catenin. Interestingly, pretreatment with jorunnamycin A at 0.5 μM for 24 h considerably sensitized lung CSCs to cisplatin-induced apoptosis, as evidenced by upregulated p53 and decreased Bcl-2 in jorunnamycin A-pretreated CSC-enriched spheroids. Moreover, the combination treatment of jorunnamycin A (0.5 μM) and cisplatin (25 μM) also diminished CD133-overexpresssing cells presented in CSC-enriched spheroids. Thus, evidence on the regulatory functions of jorunnamycin A may facilitate the development of this marine-derived compound as a novel chemotherapy agent that targets CSCs in lung cancer treatment.

show abstract

Epigenetic activation of FOXF1 confers cancer stem cell properties to cisplatin‑resistant non‑small cell lung cancer

Cited by 11 publications

References 40 publications

Emerging biomarker associated with prognosis of prostate cancer identified via co-expression analysis

Emerging biomarker associated with prognosis of prostate cancer identified via co-expression analysis

miR-26a-5p Suppresses Wnt/β-Catenin Signaling Pathway by Inhibiting DNMT3A-Mediated SFRP1 Methylation and Inhibits Cancer Stem Cell-Like Properties of NSCLC

Jorunnamycin A Suppresses Stem-Like Phenotypes and Sensitizes Cisplatin-Induced Apoptosis in Cancer Stem-Like Cell-Enriched Spheroids of Human Lung Cancer Cells

Contact Info

Product

Resources

About