ZFX promotes tumorigenesis and confers chemotherapy resistance in esophageal squamous cell carcinoma

Wu, Jingjing; Zhou, Yu; Wang, Tao; Jiang, Chao; Gao, Yong; Wei, Bin

doi:10.1016/j.clinre.2020.101586

Cited by 5 publications

(2 citation statements)

References 32 publications

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“…However, the key genes associated with chemotherapyresistance in ESCC are not fully understood. Several published works have demonstrated that this resistance could be affected by both mRNAs, including taurine upregulated 1 (TUG1), zinc finger protein x-linked (ZFX), and nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and miRNAs, such as miR-130a-3p, miR-148a-3p, miR-125a-5p, and miR-224 (17)(18)(19)(20)(21). Herein, we discovered that hsa-miR-18a-3p, hsa-miR-935, hsa-miR-1226-3p, and hsa-miR-99b-5p were downregulated in resistant ESCC cells, and for the first time, that some novel targets, including DOCK8, GNB4, CACNB2, and SCN1A, were possibly highly involved in ESCC chemotherapy resistance.…”

Section: Discussionmentioning

confidence: 99%

Analysis of cancer-promoting genes related to chemotherapy resistance in esophageal squamous cell carcinoma

Xie¹,

Zhang²,

Qian³

et al. 2022

Ann Transl Med

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Background: According to histopathology, esophageal cancer can be divided into squamous cell carcinoma (SCC) and esophageal adenocarcinoma (adeno arcinoma). In China, 90% of esophageal cancer patients are squamous cell carcinoma. Cisplatin and fluaziridine are the main chemotherapy before and after surgery.Long-term drug treatment is often accompanied by the emergence of drug resistance of tumor cells. There are many mechanisms for the emergence of drug resistance of tumor cells, including the increase of drug efflux, the decrease of drug intake, the inhibition of cell apoptosis, and so on. This study aimed to investigate the key cancer-promoting genes related to chemotherapy resistance in esophageal squamous cell carcinoma (ESCC).Methods: Two datasets from the Gene Expression Omnibus (GEO) database (GSE86099 and GSE50224) were retrieved. We performed microRNA (miRNA) and messenger RNA (mRNA) expression analysis to identify differentially expressed genes (DEGs). The intersection of the downregulated miRNA targets and the upregulated mRNAs were used for Gene Ontology (GO) enrichment analysis, and survival risk was assessed using data from The Cancer Genome Atlas (TCGA).Results: There were 35 common genes, of which, based on GO enrichment, most were related to the cardiac muscle cell action. Four genes showed significant association with the estimated half-maximal inhibitory concentration (IC 50 ) of paclitaxel: bone morphogenetic protein 1 (BMP1), dumbbell former 4 protein (DBF4), angiogenin (ANG), and MAP7 domain containing 2 (MAP7D2). Four risk factors (MP1, HIP1, ANG, and MAP7D2) were selected to generate a signature using least absolute shrinkage and selection operator (LASSO) regression. Protein-protein interaction (PPI) analysis showed guanine nucleotide-binding protein subunit beta 4 (GNB4), calcium voltage-gated channel auxiliary subunit beta 2 (CACNB2), and sodium voltage-gated channel alpha subunit 1 (SCN1A) were located at key positions of the network. Among potential risk genes, only the high expression of dedicator of cytokinesis 8 (DOCK8) was associated with poorer survival. Conclusions:The 35 oncogenes may be involved in mechanisms of chemotherapy resistance in ESCC, as well as the corresponding enrichment and regulatory network. The signature containing 4 key risk genes merits further investigation and may provide a deeper understanding of the molecular mechanisms in ESCC treatment failure.

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Section: Discussionmentioning

confidence: 99%

Analysis of cancer-promoting genes related to chemotherapy resistance in esophageal squamous cell carcinoma

Xie¹,

Zhang²,

Qian³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…For example, known ESCC-related miRNAs include miR-23b-5p, miR-877-3p, and miR-17-92, among others (13)(14)(15)(16). Several published works demonstrated that chemotherapy resistance can be affected by mRNAs like TUG1, ZFX, and NRF2, and miRNAs like miR-130a-3p, miR-125a-5p, and miR-224 (17)(18)(19)(20)(21). However, the key prognostic molecules in the therapeutic mechanism of ESCC, especially in nCRT, still need to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Use of exosome transcriptome-based analysis to identify novel biomarkers in patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy

Yang¹,

Zhang²,

Liu³

et al. 2023

Ann Transl Med

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Background: The prognosis of esophageal squamous cell carcinoma (ESCC) is improved by neoadjuvant chemoradiotherapy (nCRT), especially for patients with pathologic complete response (pCR). Despite the efforts to predict treatment response using multimodality, no molecule has proven to be a strong biomarker.This study aimed to profile the expression of exosome transcriptome that could predict pCR in ESCC before and after nCRT.Methods: We collected paired blood samples of 15 patients with ESCC who received nCRT and radical surgery. They were divided into 3 groups: (A) residual tumor in the first clinical response evaluation (CRE-1), (B) no residual tumor in CRE-1 but with residual tumor in CRE-2 which was performed after 5-6 weeks, and (C) no residual tumor in CRE-1 or CRE-2. For each patient, the blood sample was collected before nCRT (time point 0); and then 6 weeks after nCRT, the clinical response was evaluated, and another blood sample was collected (time point 1).Results: Using the intersection of different sets, we found 23 progression-associated messenger RNAs (mRNAs) and 67 remission-associated mRNAs. Between remission-associated mRNAs and the targets of progression-associated (carcinogenic) microRNAs (miRNAs), the intersection was acquired, and 2 miRNA-mRNA networks (IFIT2-miR-3615-IFIT2-miR-484 and BTN3A3-miR-6803-3p) were identified. Among the intersection of progression-associated (carcinogenic) mRNAs and the targets of remission-associated miRNAs, there is a network with miR-132-3p (remission-associated miRNA) located at the core, matched with DICER1, KLHL8, ANKRD12, ASH1L, and IMP4.Conclusions: Our findings identified altered plasma exosome RNAs among the different groups and between different time points of nCRT, as well as the corresponding enrichments and regulatory networks, which may serve as potentially predictors of treatment response for patients with ESCC after nCRT.

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Silencing of LINC01278 promotes sensitivity of non-small cell lung cancer cells to osimertinib by targeting miR-324-3p/ZFX axis

Lei,

Liu,

Guan

et al. 2024

Cytotechnology

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ZFX promotes tumorigenesis and confers chemotherapy resistance in esophageal squamous cell carcinoma

Cited by 5 publications

References 32 publications

Analysis of cancer-promoting genes related to chemotherapy resistance in esophageal squamous cell carcinoma

Analysis of cancer-promoting genes related to chemotherapy resistance in esophageal squamous cell carcinoma

Use of exosome transcriptome-based analysis to identify novel biomarkers in patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy

Silencing of LINC01278 promotes sensitivity of non-small cell lung cancer cells to osimertinib by targeting miR-324-3p/ZFX axis

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