Tripartite motif-containing 15 overexpression in non-small cell lung cancer is associated with poor patient prognoses

Han, Xiaoying; Huang, Can; Qu, Xiao; Liu, Shaorui; Yang, Xudong; Wang, Yu; Bie, Fenglong; Liu, Qi; Du, Jiajun

doi:10.7150/jca.27856

Cited by 19 publications

(12 citation statements)

References 34 publications

(26 reference statements)

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“…IHC was performed as described previously 37 . Briefly, tissue sections underwent deparaffinization in xylene, followed by rehydration through graded ethanol at room temperature, which then were heated in a 1 mmol/L ethylenediaminetetraacetic acid (EDTA) buffer (water bath, 96–98 °C) for 15 min for antigen retrieval.…”

Section: Methodsmentioning

confidence: 99%

The double inhibition of PDK1 and STAT3-Y705 prevents liver metastasis in colorectal cancer

Qin

Tian

Zhang

et al. 2019

Sci Rep

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As a key glycolysis enzyme, the significance of pyruvate dehydrogenase kinase 1 (PDK1) in the development of colorectal cancer (CRC) remains unknown. This study revealed that the prognosis of CRC patients with high levels of PDK1 was poor, and PDK1 knockdown significantly reduced liver metastasis of CRC in both nude mice and immune competent BALB/C mice. When combined with cryptotanshinone (CPT), an inhibitor of STAT3-p-Y705, the liver metastasis was further inhibited. PDK1 knockdown obviously increased reactive oxygen species level in anoikis conditions and subsequently resulted in an elevated anoikis, but the combination of PDK1 knockdown and CPT showed a reduced effect on anoikis. Based on this discrepancy, the adherence ability of CRC cells to matrix protein fibronectin was further detected. It showed that PDK1 knockdown significantly decreased the adherence of CRC cells to fibronectin when combined with CPT. These results suggest that inhibition of PDK1 can decrease the surviving CRC cells in blood circulation via up-regulation of anoikis, and inhibition of STAT3-p-Y705 can prevent it to settle down on the liver premetastatic niche, which ultimately reduces liver metastasis.

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Section: Methodsmentioning

confidence: 99%

The double inhibition of PDK1 and STAT3-Y705 prevents liver metastasis in colorectal cancer

Qin

Tian

Zhang

et al. 2019

Sci Rep

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“…Tripartite motif (TRIM)-containing proteins are a family of approximately 70 proteins that have an N-terminal RING finger, one or two B-boxes, and a coiled-coil (CC) domain [ 16 ]. RING finger structure is closely related to E3 ubiquitin ligases activity [ 17 ]. Although not all TRIM proteins have E3 activity, TRIM proteins have attracted attentions in recent years from E3 research field [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells

et al. 2022

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The incidence of lung cancer is increasing worldwide. Although great progress in lung cancer treatment has been made, the clinical outcome is still unsatisfactory. Tripartite motif (TRIM)-containing proteins has been shown to be closely related to tumor progression. However, the function of TRIM46 in lung cancer is largely unknown. Here, TRIM46 amplification was found in lung adenocarcinoma (LUAD) tissues and TRIM46 amplification was significantly associated with a poor survival rate. Overexpression of wild type TRIM46 increased the proliferation of LUAD cells and glycolysis, promoted xenografts growth, and enhanced cisplatin (DDP) resistance of LUAD cells via increased ubiquitination of pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) and upregulation of p-AKT. In contrast, overexpression of RING-mutant TRIM46 did not show any effects, suggesting the function of TRIM46 was dependent on the E3 ligase activity. Furthermore, we found that TRIM46 promoted LUAD cell proliferation and DDP resistance by enhancing glycolysis. PHLPP2 overexpression reversed the effects of TRIM46 overexpression. Amplification of TRIM46 also promoted LUAD growth and enhanced its DDP resistance in a patient-derived xenograft (PDX) model. In conclusion, our data highlight the importance of TRIM46/PHLPP2/AKT signaling in lung cancer and provide new insights into therapeutic strategies for lung cancer.

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“…The candidate genes were DKK1, EXT1, KIAA1324 and TRIM15. Among these genes, DKK1 has been widely reported for its prognostic value in NSCLC, 9 and prognostic value of TRIM15 has been emphasized 10 . Although the effect of KIAA1324 was also reported in NSCLC 11 .…”

Section: Resultsmentioning

confidence: 99%

“…Among these genes, DKK1 has been widely reported for its prognostic value in NSCLC, 9 and prognostic value of TRIM15 has been emphasized. 10 Although the effect of KIAA1324 was also reported in NSCLC. 11 Thus, the EXT1 DNA methylation and its function were studied in this work.…”

Section: Identification Of Genes On Methylationexpression-prognosis Axis For Nsclcmentioning

confidence: 99%

EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non‐small cell lung carcinoma via WNT signalling pathway

Kong¹,

Chen²,

Zhao³

et al. 2021

J Cellular Molecular Medi

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DNA methylation is important for lung cancer prognosis. In this work, it is aimed to seek novel biomarkers with DNA methylation‐expression‐pathway pattern and explore its underlying mechanism. Prognostic DNA methylation sites and mRNAs were screened in NSCLC data set from TCGA, and further validated using the samples retrospectively collected, and EXT1 was identified as a potential target. Gene body methylation of three CpG sites (cg03276982, cg11592677, cg16286281) on EXT1 was significantly associated with clinical outcome, and the EXT1 gene expression also predicted prognosis. The expression level of EXT1 was also correlated with its DNA methylation level. This observation was further validated in a new data set consist of 170 samples. Knocking down of EXT1 resulted in decreased proliferation and migration. EXT1 targets were analysed using GSEA. It is found that the WNT signalling is the potential downstream target of EXT1. Further analyses revealed that the EXT1 targets the beta‐catenin and effect migration rate of NSCLC cell lines. The WNT signalling inhibitor, XAV‐939, effectively disrupted the migration promotion effect induced by EXT1. In summary, EXT1 methylation regulates the gene expression, effects the proliferation and migration via WNT pathway and predicted a poor prognosis for NSCLC.

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Tripartite motif-containing 15 overexpression in non-small cell lung cancer is associated with poor patient prognoses

Cited by 19 publications

References 34 publications

The double inhibition of PDK1 and STAT3-Y705 prevents liver metastasis in colorectal cancer

The double inhibition of PDK1 and STAT3-Y705 prevents liver metastasis in colorectal cancer

TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells

EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non‐small cell lung carcinoma via WNT signalling pathway

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