XPA serves as an autophagy and apoptosis inducer by suppressing hepatocellular carcinoma in a PI3K/Akt/mTOR dependent manner

Deng, Yi Zhen; Chen, Qingsong; Huang, Weifeng; Dai, Jiangwen; Wu, Zhongjun

doi:10.21037/jgo-21-310

Cited by 7 publications

(6 citation statements)

References 35 publications

(35 reference statements)

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“…It is established that the PI3K/Akt/mTOR signaling pathway is implicated in HCC progression [ 15 , 16 , 17 ]. Thus, we examined whether PI3K/Akt/mTOR signaling could be modulated by PSMB5.…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, it was found out that the downregulation of PSMB5 significantly reduced the phosphorylation level of proteins for the PI3K/Akt/mTOR signaling pathway. A study by Deng et al [16] showed that the overexpression of XPA not only inhibits proliferation, migration and invasion in HCC, but also suppresses the expression of p-PI3K, p-Akt and p-mTOR. Luo et al [17] revealed that YTHDF1 promoted the proliferation of HCC cells by activating the PI3K/Akt/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…A study by Deng et al . [ 16 ] showed that the overexpression of XPA not only inhibits proliferation, migration and invasion in HCC, but also suppresses the expression of p‐PI3K, p‐Akt and p‐mTOR. Luo et al .…”

Section: Discussionmentioning

confidence: 99%

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PSMB5 overexpression is correlated with tumor proliferation and poor prognosis in hepatocellular carcinoma

Liu

et al. 2022

FEBS Open Bio

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Aberrant expression of members of the proteasome subunit beta (PSMB) family (including PSMB2, PSMB4, PSMB7 and PSMB8) has been reported in hepatocellular carcinoma (HCC). However the role of PSMB5 in HCC is unclear. To address this issue, we examined the expression of PSMB5 in HCC tissues using the The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus databases. A quantitative real‐time PCR and immunohistochemistry were performed to validate the expression of PSMB5 in HCC. The survival mutation status and immune cell infiltration of PSMB5 were also evaluated in HCC. We then examined the effect of knocking down PSMB5 expression through RNA interference in the HCC cell line Huh7. High expression of PSMB5 was observed in HCC tissues and was associated with poor prognosis. PSMB5 expression and clinical characteristics were then incorporated to build a prognostic nomogram. We observed that PSMB5 expression was closely related to the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cell macrophages and neutrophils. Moreover silencing of PSMB5 in Huh7 significantly suppressed cell proliferation and migration at the same time as increasing apoptosis. Inhibition of the phosphatidylinositol‐3‐kinase/Akt/mechanistic target of rapamycin pathway was observed after PSMB5 downregulation in Huh7 cells. Our findings suggest that PSMB5 may promote the proliferation of HCC cells by inactivating the phosphatidylinositol‐3‐kinase/Akt/mechanistic target of rapamycin signaling pathway and thus PSMB5 may have potential as a biomarker for diagnosis and prognosis of HCC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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PSMB5 overexpression is correlated with tumor proliferation and poor prognosis in hepatocellular carcinoma

Liu

et al. 2022

FEBS Open Bio

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“…Cheng et al showed that the long non-coding RNA RP11-241J12.3 targeting pyruvate carboxylase promotes invasiveness of HCC by disrupting pyruvate metabolism and DNA mismatch repair system ( 38 ). Through the activation of PI3K/Akt/mTOR, XPA suppressed the growth of cancer cells inside the liver by promoting autophagy and cell death ( 39 ). Additionally, a study has found that inhibiting RFX6 through the Notch pathway inhibits the invasive ability of tumor cells and affects tumor immunity in HCC ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Glycolysis-related gene dihydrolipoamide acetyltransferase promotes poor prognosis in hepatocellular carcinoma through the Wnt/β-catenin and PI3K/Akt signaling pathways

Zhou¹,

Gu²,

Shao³

et al. 2022

Ann Transl Med

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Background: Recent research suggests that dihydrolipoamide acetyltransferase (DLAT), which is a copperinduced cell death-related gene, is involved in multiple biological events in tumors. This study sought to investigate the relationship between DLAT and hepatocellular carcinoma (HCC).Methods: In the Cancer Genome Atlas (TCGA) database, we first identified the differentially expressed gene (i.e., DLAT), then confirmed DLAT expression, and found a link between it and the prognosis of HCC patients. An internal validation nomogram was built based on a multivariate Cox regression analysis.Data from the Tumor Immune Estimation Resource (TIMER) database was used to examine the association between DLT and immunological cells. A gene set enrichment analysis (GSEA) was conducted to investigate the probable mechanism of action. Finally, in vitro cytological research was conducted to further examin the involvement of DLAT in HCC-related unfavorable biological events. Results:The database screenings showed that DLAT was a differentially expressed molecule; that is, DLAT was more highly expressed in the cancer tissues than normal tissues. TCGA results and Kaplan-Meier-plotter data sets showed that HCC patients with reduced DLAT expression had greater diseasespecific survival (DSS), overall survival (OS), and progression-free interval (PFI). The prediction model had a concordance index of 0.659 (0.614-0.704), which indicates high accuracy. According to the TIMER database, tumor cells in the HCC microenvironment may be able to bypass the immune system due to the expression of DLAT. The in vitro cytological tests showed that DLAT knockdown significantly decreased the proliferation and invasion of the HCC cells. It also inhibited the activity of the phosphatidylinositol-4,5bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and Wnt/β-catenin signaling pathways.Conclusions: Decreased DLAT expression significantly prolongs the OS, PFI, and DSS of HCC patients.DLAT may be employed as a new predictive biomarker for HCC, and may be linked to the immune system in HCC patients. The tumor microenvironment (TME) may have a significant effect on the ability of tumor cells to evade the immune system. The PI3K/Akt and Wnt/β-catenin signaling pathways may affect the prognosis of HCC by interfering with DLAT. Given these findings, HCC may be an ideal target for the development of anti-cancer therapies.

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“…This gene has been shown to promote apoptosis in response to DNA damage, in addition to its role in nucleotide excision repair 29 . Moreover, downregulation of XPA has been associated with decreased patient survival in colorectal cancer 30 .…”

Section: Somatic Mutations In Cleavage and Polyadenylation Signals Ca...mentioning

confidence: 99%

Recurrent disruption of tumour suppressor genes in cancer by somatic mutations in cleavage and polyadenylation signals

Kainov,

Hamid,

Makeyev

2024

Preprint

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The expression of eukaryotic genes relies on the precise 3’-terminal cleavage and polyadenylation of newly synthesized pre-mRNA transcripts. Defects in these processes have been associated with various diseases, including cancer. While cancer-focused sequencing studies have identified numerous driver mutations in protein-coding sequences, noncoding drivers – particularly those affecting the cis-elements required for pre-mRNA cleavage and polyadenylation – have received less attention. Here, we systematically analysed cancer somatic mutations affecting 3’UTR polyadenylation signals using the Pan-Cancer Analysis of Whole Genomes (PCAWG) dataset. We found a striking enrichment of cancer-specific somatic mutations that disrupt strong and evolutionarily conserved cleavage and polyadenylation signals within tumour suppressor genes. Further bioinformatics and experimental analyses conducted as a part of our study suggest that these mutations have a profound capacity to downregulate the expression of tumour suppressor genes. Thus, this work uncovers a novel class of noncoding somatic mutations with significant potential to drive cancer progression.

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XPA serves as an autophagy and apoptosis inducer by suppressing hepatocellular carcinoma in a PI3K/Akt/mTOR dependent manner

Cited by 7 publications

References 35 publications

PSMB5 overexpression is correlated with tumor proliferation and poor prognosis in hepatocellular carcinoma

PSMB5 overexpression is correlated with tumor proliferation and poor prognosis in hepatocellular carcinoma

Glycolysis-related gene dihydrolipoamide acetyltransferase promotes poor prognosis in hepatocellular carcinoma through the Wnt/β-catenin and PI3K/Akt signaling pathways

Recurrent disruption of tumour suppressor genes in cancer by somatic mutations in cleavage and polyadenylation signals

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