CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer

Wu, Yi-Ying; Hwang, Yi Ting; Perng, Wann Cherng; Chian, Chih-Feng; Ho, Ching Liang; Lee, Shih Chun; Chang, Hung; Terng, Harn Jing; Chao, Tsu Yi

doi:10.1016/j.jfma.2016.01.009

Cited by 16 publications

(9 citation statements)

References 39 publications

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“…To some extent, te present study is consistent with our study. By contrast, Wu et al ( 26 ) demonstrated that IRF4 was a protective prognostic factor in NSCLC patients. These contradictory data may suggest that IRF4 may reflect tumor-infiltrating lymphocyte activity in tissue section.…”

Section: Discussionmentioning

confidence: 91%

Interferon regulatory factor 4 (IRF4) is overexpressed in human non-small cell lung cancer (NSCLC) and activates the Notch signaling pathway

Qian

Xing

et al. 2017

Molecular Medicine Reports

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The transcription factor, interferon regulatory factor 4 (IRF4), serves an essential role in the regulation of immune responses, and has been reported to act as a diagnostic and prognostic marker for various hematological malignancies. The present study aimed to investigate whether IRF4 could exert effects on human non-small cell lung cancer (NSCLC) and to explore the underlying mechanism. The mRNA and protein expression of IRF4 was detected in NSCLC tissues using reverse-transcription quantitative polymerase chain reaction and western blotting, respectively. In the in vitro experiment, IRF4 expression was knocked down or overexpressed using lentivirus in human lung adenocarcinoma A549 and lung squamous cell carcinoma LC-AI cell lines. Cell proliferation and colony number were analyzed using MTT and colony formation assays, respectively. The expression levels of IRF4 mRNA and protein were significantly higher in NSCLC tissues (n=54) compared with that in adjacent non-tumor tissues. Similarly, the expression levels of Notch1 and Notch2 mRNA were significantly higher in NSCLC tissues. Furthermore, the expression level of IRF4 mRNA was positively correlated with the levels of Notch1 and Notch2 mRNA in NSCLC tissues. Consequently, using NSCLC cell lines, it was demonstrated that the knockdown of IRF4 expression significantly reduced the cell proliferation rate and colony formation, whereas IRF4-overexpression significantly increased them. Notably, the IRF4 knockdown significantly decreased the expression levels of Notch1 and Notch2 mRNA, and phosphorylated protein kinase B (AKT), whereas IRF4 overexpression resulted in the opposite. The results of the present study indicate that IRF4 is overexpressed and serves as a tumor promoter in human NSCLC, at least partially, through activating the Notch-Akt signaling pathway.

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Section: Discussionmentioning

confidence: 91%

Interferon regulatory factor 4 (IRF4) is overexpressed in human non-small cell lung cancer (NSCLC) and activates the Notch signaling pathway

Qian

Xing

et al. 2017

Molecular Medicine Reports

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“…IRF-4, as a member of the interferon regulating factor family of transcription factors, is considered to be an oncogene in lymphoid malignancy and multiple myeloma[26]. Notably, recent studies have demonstrated that IRF-4 is a tumor suppressor in breast cancer[27] and lung cancer[28]. The homeodomain transcription factor CDX-2 has been investigated in colon cancer by many studies, which have suggested that CDX-2 loss is associated with the poor prognosis of colon cancer[29-32].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA PIP5K1A promotes colon cancer development through inhibiting miR-1273a

Qu¹,

Zhang²,

Ma³

et al. 2019

WJG

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BACKGROUNDCircular RNAs (circRNAs) are considered to be highly stable due to the closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. Colon cancer is one of the most common malignancies worldwide. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A’s role may help with the identification of novel diagnostic and therapeutic targets for colon cancer.AIMTo investigate the status of circPIP5K1A in colon cancers and its effects on the modulation of cancer development.METHODSThe expression level of circPIP5K1A in tissue and serum samples from colon cancer patients, as well as human colonic cancer cell lines was detected by real-time quantitative reverse transcription-polymerase chain reaction. Following the transfection of specifically synthesized small interfering RNA (siRNA) into colon cell lines, we used Hoechst staining assay to measure the ratio of cell death in the absence of circPIP5K1A. Moreover, we also used the Transwell assay to assess the migratory function of colon cells overexpressing circPIP5K1A. Additionally, we employed a series of bioinformatics prediction programs to predict the potential of circPIP5K1A-targeted miRNAs and mRNAs. The miR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Afterwards, the expression of activator protein 1 (AP-1), interferon regulating factor 4 (IRF-4), caudal type homeobox 2 (CDX-2), and zinc finger of the cerebellum 1 (Zic-1) was detected by western blotting.RESULTSCircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. Knockdown of circPIP5K1A in colon cancer cells impaired cell viability and suppressed cell invasion and migration, while enforced expression of circPIP5K1A exhibited the opposite effects on cell migration. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Subsequent studies showed that overexpression of circPIP5K1A augmented the expression of AP-1 but attenuated the expression of IRF-4, CDX-2, and Zic-1. Reciprocally, overexpression of miR-1273a abrogated the oncogenic function of circPIP5K1A in colon cancers.CONCLUSIONOverall, our data demonstrate the oncogenic role of circPIP5K1A-miR-1273a axis in regulation of colon cancer development, which provides a novel insights into colon cancer pathogenesis.

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“…However, a study by Wu et al. indicated that IRF4 from peripheral mononuclear cells has a protective role in advanced NSCLC patients with 77.30% adenocarcinoma and 8.51% squamous cell carcinoma ( 14 ). Taken together these controversial conclusions and our findings, we speculated that the prognostic impact on IRF4 was likely associated with the different sample sources (tumor cell or lymphocyte) in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Using the tumor tissues from 125 NSCLC patients with surgical resection, Chen et al described that IRF4 was an unfavorable prognostic factor in NSCLC (13). But another study demonstrated that high IRF4 expression in NSCLC patients' peripheral blood was significantly associated with longer survival (14). Until now, there was no study focused on the specific subtypes of NSCLC to explore the prognostic role of IRF4.…”

Section: Introductionmentioning

confidence: 99%

Interferon Regulatory Factor 4 Correlated With Immune Cells Infiltration Could Predict Prognosis for Patients With Lung Adenocarcinoma

Zhai

Zhang

et al. 2021

Front. Oncol.

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BackgroundImmune related interferon regulatory factor 4 (IRF4) is a member of the IRF family, whereas the clinical significance and possible role of IRF4 in lung adenocarcinoma (LUAD) remains unclear. We aimed to investigate the role of IRF4 in predicting the prognosis of LUAD patients.MethodsUsing The Cancer Genome Atlas (TCGA) database and our immunohistochemical (IHC) cohort, we analyzed the correlation between IRF4 expression and clinical characteristics, and the prognostic value of IRF4 was also evaluated in LUAD. The potential biological functions of IRF4 in LUAD were analyzed by Gene Set Enrichment Analysis (GSEA). The relationship between IRF4 and immune cell infiltration were evaluated by TISIDB database and our own IHC cohort. In addition, an immune checkpoint inhibitor (ICI) treated cohort from Gene Expression Omnibus database was used to determine the role of IRF4 in LUAD patients with immunotherapy.ResultsWe found that either mRNA or protein expression level of IRF4 was significantly higher in LUAD than in normal tissues (P < 0.001). The elevate in IRF4 expression in LUAD was significantly associated with the earlier clinical stage (P = 0.002). Patients with LUAD and IRF4 high expression correlated with significant longer overall survival in both TCGA database (P < 0.05) and our IHC-cohort (P = 0.001). Our results also demonstrated that IRF4 could serve as an independent favorable prognostic factor in patients with LUAD. GSEA analysis indicated that high IRF4 expression group enriched with several immune-related pathways, such as B cell receptor signaling pathway, T cell receptor signaling pathway and cytokine-cytokine receptor interaction signaling pathway. In LUAD, IRF4 positively correlated with several different immune infiltrations including various B cells, CD8+ T cells and CD4+ T cells both in mRNA and protein levels. Additionally, we found that the expression of IRF4 was positively associated with PD-1 and PD-L1 mRNA expression levels, and IRF4 high expression predicted moderate better survival in LUAD with immunotherapy (P = 0.071).ConclusionsOur results suggested that IRF4 was associated with higher B cells and T cells infiltration levels and might be a favorable prognostic biomarker in LUAD patients, whereas the potential prognostic role of IRF4 in ICI-treated patients needed further exploration.

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CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer

Abstract: Molecular signatures in PB can stratify the prognosis in patients with advanced NSCLC. Further prospective, interventional clinical trials should be performed to test if gene profiling also predicts resistance to chemotherapy.

Cited by 16 publications

References 39 publications

Interferon regulatory factor 4 (IRF4) is overexpressed in human non-small cell lung cancer (NSCLC) and activates the Notch signaling pathway

Interferon regulatory factor 4 (IRF4) is overexpressed in human non-small cell lung cancer (NSCLC) and activates the Notch signaling pathway

Circular RNA PIP5K1A promotes colon cancer development through inhibiting miR-1273a

Interferon Regulatory Factor 4 Correlated With Immune Cells Infiltration Could Predict Prognosis for Patients With Lung Adenocarcinoma

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