T-box 3 overexpression is associated with poor prognosis of non-small cell lung cancer

Wu, Yueming; Jiang, Feng; Zhang, Yawei

doi:10.3892/ol.2017.5855

Cited by 6 publications

(5 citation statements)

References 20 publications

(30 reference statements)

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“…As HYAL1 was reported to have no effect on p53-mediated cell death [26], our finding suggests a novel and indirect association between HYAL1 and p53 through DACH1 regulation. TRIM24, TBX3, and KHDRBS1 were upregulated in lung cancer [44][45][46]. Hence, we noted their significant downregulation in HYAL1-overexpressed HFL-1 cells, which is consistent with their role in inducing fibroproliferation.…”

supporting

confidence: 84%

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

Dong

Huang

et al. 2020

BioMed Research International

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Background. Idiopathic pulmonary fibrosis (IPF), the most common interstitial lung disease, arises from transforming growth factor beta 1- (TGFβ1-) induced aberrant fibroproliferation in response to epithelial injury. The TGFβ1 antagonists—hyaluronidases (HYALs)—have been used to clinically treat pulmonary fibrosis. This study focused on characterizing the effect of HYAL1, the main enzyme in hyaluronan degradation, on human lung fibroblast proliferation and apoptosis, and elucidating its potential underlying mechanism of action. Methods. We first performed microarray data mining of previously published gene expression datasets to identify key gene signatures in IPF lung tissues. HYAL1 expression levels in IPF and normal lung tissues were then characterized using immunohistochemistry followed by real-time quantitative reverse transcription-PCR (qRT-PCR) and western blot analysis on isolated fibroblasts from fresh lung tissues of IPF and healthy donors. A human fetal lung fibroblast HFL-1 cell line, which was used in place of primary lung fibroblasts, was used to assess the proliferative or apoptotic effects associated with lentiviral-induced HYAL1 overexpression using CCK-8 cell proliferation assay and Annexin V-APC staining. The identification of potentially associated molecular pathways was performed using microarray analysis followed by qRT-PCR and western blot analysis. Results. Lung tissue microarray data mining and immunohistochemistry revealed significantly downregulation of HYAL1 in IPF lung tissue. However, HYAL1 expression level in IPF fibroblasts was significantly upregulated at the mRNA level, but not altered at the protein level. HYAL1 overexpression in HFL-1 fibroblasts reduced fibroproliferation modestly but did not promote apoptosis. In addition, HYAL1 overexpression led to concomitant transcription factor downregulation, bone morphogenetic protein receptor 2 (BMPR2) signaling activation, but had no effect on TGFβ receptor 2 (TGFβR2) signaling. Conclusions. We showed that HYAL1 overexpression could prevent HFL-1 fibroproliferation. Furthermore, our findings suggest that transcriptional regulators and BMP receptor signaling may be involved in HYAL1 modulation in IPF therapy.

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supporting

confidence: 84%

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

Dong

Huang

et al. 2020

BioMed Research International

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“…Our findings on suppressed expression of TBX2 subfamily in NSCLC are also in congruence with various recent reports implicating tumor suppressive properties for members of the TBX2 subfamily. While the report by Wu et al [ 41 ] showed that TBX3 is up-regulated in NSCLC, the same study demonstrated that a fraction of NSCLCs show reduced expression of the gene. Low expression of TBX4 gene was reported to be associated with worse prognosis among patients with stage II pancreatic ductal adenocarcinoma [ 48 ].…”

Section: Discussionmentioning

confidence: 91%

“…by quantitative real-time PCR) in NSCLCs and paired normal lung tissues in a smaller subset of NSCLC cases ( n = 40 to 50) [ 39 , 40 ] demonstrating that the gene is elevated in the tumors. These earlier studies [ 39 – 41 ], albeit few, point to putative oncogenic roles and properties for the TBX2 gene in human NSCLC. In contrast, our findings, collectively, revealed that the TBX2 gene is markedly suppressed in NSCLC relative to normal lung from four publicly available expression datasets [ 23 – 26 ] ( Supplementary Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

TBX2subfamily suppression in lung cancer pathogenesis: a high-potential marker for early detection

et al. 2017

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The TBX2 subfamily (TBXs 2, 3, 4 and 5) transactivates or represses genes involved in lung organogenesis. Yet TBX2 subfamily expression in pathogenesis of non-small cell lung cancer (NSCLC), the most common lung malignancy, remains elusive. We sought to probe the expression profile of the TBX2 subfamily in early phases of NSCLC. Expression of TBX2 subfamily was analyzed in datasets of pan-normal specimens as well as NSCLCs and normal lung tissues. TBX2 subfamily expression in matched normal lungs, premalignant hyperplasias and NSCLCs was profiled by transcriptome sequencing. TBX2 subfamily expression was evaluated in the cancerization field consisting of matched NSCLCs and adjacent cytologically-normal airways relative to distant normal lungs and in a dataset of normal bronchial samples from smokers with indeterminate nodules suspicious for malignancy. Statistical analysis was performed using R. TBX2 subfamily expression was markedly elevated in normal lungs relative to other organ-specific normal tissues. Expression of the TBXs was significantly suppressed in NSCLCs relative to normal lungs (P < 10−9). TBX2 subfamily was significantly progressively decreased across premalignant lesions and NSCLCs relative to normal lungs (P < 10−4). The subfamily was significantly suppressed in NSCLCs and adjacent normal-appearing airways relative to distant normal lung tissues (P < 10−15). Further, suppressed TBX2 subfamily expression in normal bronchi was associated with lung cancer status (P < 10−5) in smokers. Our findings suggest that the TBX2 subfamily is notably suppressed in human NSCLC pathogenesis and may serve as a high-potential biomarker for early lung cancer detection in high-risk smokers.

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“…EGFR -amp demonstrated a much higher rate in paired CSF samples (8/22, 36%) than in the PLA samples (1/22, 5%). Overexpression of TBX3 is uniquely associated with tumor size, and inactivation of PTEN is notably associated with poor survival in NSCLC patients [ 11 , 12 ]. The detection rates of TBX3 and PTEN in CSF were almost double those of the paired PLA samples ( Figure 3 C), making the liquid CSF medium an ideal candidate for categorizing patients treated with EGFR -TKI.…”

Section: Resultsmentioning

confidence: 99%

Cerebrospinal fluid-derived circulating tumor DNA is more comprehensive than plasma in NSCLC patients with leptomeningeal metastases regardless of extracranial evolution

Yang

Wen

Zhao

et al. 2022

Heliyon

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T-box 3 overexpression is associated with poor prognosis of non-small cell lung cancer

Cited by 6 publications

References 20 publications

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

TBX2subfamily suppression in lung cancer pathogenesis: a high-potential marker for early detection

Cerebrospinal fluid-derived circulating tumor DNA is more comprehensive than plasma in NSCLC patients with leptomeningeal metastases regardless of extracranial evolution

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