Overexpression of Karyopherin Subunit alpha 2 (KPNA2) Predicts Unfavorable Prognosis and Promotes Bladder Cancer Tumorigenicity via the P53 Pathway

Shi, Changlong; Sun, Li; Liu, Shaozhuang; Zhang, Enchong; Song, Yun‐Chun

doi:10.12659/msm.921087

Cited by 9 publications

(9 citation statements)

References 44 publications

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“…This outcome could be influenced by different data processing or updated survival information. Thus, we further used, OncoLnc (http://www.oncolnc.org/) and the Kaplan Meier plotter method (27,28) to further update and analyze these data, the final results were consistent with the results of our study.…”

Section: Discussionsupporting

confidence: 75%

A pan-cancer analysis of the oncogenic role of Keratin 17 (KRT17) in human tumors

Li¹,

Teng²,

Wu³

et al. 2021

Transl Cancer Res TCR

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Background Although new evidence from cells or animals suggests a relationship between Keratin 17 ( KRT17 ) and cancer, no pan-cancer analysis is currently available. Methods The expression level of KRT17 in generalized carcinoma was detected by the Tumor Immune Estimation Resource, version 2 (TIMER2) database, and then verified the protein expression of KRT17 in different cancer species in UALCAN database, and analyzed the relationship between the expression level of KRT17 and the clinical stage and survival of different cancers. We further explored the genetic variation of KRT17 in different tumor types included in The Cancer Genome Atlas (TCGA) and the specific mutations in each domain. The changes of KRT17 protein phosphorylation levels and protein expression levels at different phosphorylation sites in different tumors were explored. TIMER2 database was used to explore the potential relationship between the infiltration level of different immune cells and KRT17 gene expression in different TCGA cancer types. Finally, the protein binding to KRT17 and genes related to KRT17 expression were explored by STRING database and TCGA database. Results KRT17 is overexpressed in most malignancies, and we observed a distinct relationship between KRT17 expression and tumor patient prognosis. Enhanced phosphorylation levels of S13, S24, S32, and S39 were observed in several tumors, such as lung adenocarcinoma (LUAD), colon and ovarian cancers, and uterine corpus endometrial carcinoma (UCEC). Intermediate filament cytoskeleton and keratinization may be simultaneously acting with KRT17 on tumor pathogenesis. Conclusions Our pan-cancer analysis provides relatively complete information on the oncogenic functions of KRT17 in various cancers.

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Section: Discussionsupporting

confidence: 75%

A pan-cancer analysis of the oncogenic role of Keratin 17 (KRT17) in human tumors

Li¹,

Teng²,

Wu³

et al. 2021

Transl Cancer Res TCR

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“…Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these genes in DAVID showed that the involvement of KPNA2 in HCC progression was associated with p53 signaling pathway ( Figure 7a ). KPNA2 has been reported to play a tumor-promoting action in several human cancers via inactivation of p53 signaling [ 23 , 24 ]. Here, we explored whether miR-26b-5p could regulate p53 signaling by targeting KPNA2.…”

Section: Resultsmentioning

confidence: 99%

Long non-coding RNA HAGLROS facilitates tumorigenesis and progression in hepatocellular carcinoma by sponging miR-26b-5p to up-regulate karyopherin α2 (KPNA2) and inactivate p53 signaling

et al. 2022

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Hepatocellular carcinoma (HCC) is a principal histologic type of liver cancer with high mortality. Long non-coding RNAs (LncRNAs) exert a crucial role in the pathogenesis of human tumors. To date, the functions and mechanisms of lncRNA HAGLROS in HCC are rarely reported. In the current study, HAGLROS exhibited a higher level in HCC tissues and cells. HAGLROS expression was positively correlated with tumor size, TNM stage and poor clinical prognosis. Loss-of-function experiments showed that knockdown of HAGLROS significantly lowered cell proliferation, cell cycle progression, migration, invasion and epithelial to mesenchymal transition (EMT) but induced apoptosis in vitro . Consistently, tumor growth in the nude mice was effectively slowed by the depletion of HAGLROS. Mechanistically, HAGLROS could competitively bind to miR-26b-5p to prevent the suppression of miR-26b-5p on its downstream target gene Karyopherin α2 (KPNA2). Moreover, the inhibitory effects of HAGLROS knockdown on cell malignant behaviors were reversed due to the miR-26b-5p down-regulation or KPNA2 overexpression. It was interesting to note that HAGLROS inactivated p53 signaling through targeting miR-26b-5p/KPNA2. In conclusion, our results demonstrated that HAGLROS contributed to the malignant progression of HCC via serving as a sponge for miR-26b-5p to facilitate KPNA2 expression and inactivate p53 signaling. Targeting HAGLROS/miR-26b-5p/KPNA2 axis might be an alternative therapeutic strategy for HCC patients.

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“…FGF1 has been shown to inhibit p53‐dependent apoptosis and arrest cell growth 36,37 . The P53 signaling pathway plays a crucial role in tumorigenesis, as it modulates key cellular functions such as DNA damage repair, cell cycle progression, and apoptosis 38–40 …”

Section: Discussionmentioning

confidence: 99%

LRRC59 serves as a novel biomarker for predicting the progression and prognosis of bladder cancer

Zhang,

Xie,

et al. 2023

Cancer Medicine

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BackgroundLeucine‐rich repeat‐containing protein 59 (LRRC59) is an endoplasmic reticulum membrane protein involved in various cancers, but its role in bladder cancer (BC) has not been reported. The aim of the present study was to investigate the role of LRRC59 protein in BC progression and prognosis.MethodsThe expression profile and clinical significance were retrieved from BC patients in the Cancer Genome Atlas database. The methylation status of LRRC59 was analyzed by UALCAN and MethSurv databases. Potential signaling pathways and biological functions were explored by functional enrichment analysis. Immunocyte infiltration was evaluated by CIBERSORT analysis. The prognostic value of LRRC59 was evaluated by Kaplan–Meier and Cox regression analyses. Overall survival (OS) was predicted by the nomogram plot established in this study. LRRC59 expression in 10 pairs BC and adjacent noncancerous tissues were analyzed by immunohistochemistry (IHC). Cell proliferation, migration, and invasion were detected by CCK8, colony formation assay, transwell assay, and cell scratch assay, respectively. Proteins related to epithelial–mesenchymal transition and apoptosis were detected by western blot.ResultsLRRC59 overexpression significantly decreased OS, disease‐specific survival, and progress‐free interval of BC patients. LRRC59 was a prognostic marker for OS and its hypomethylation status signified a poor prognosis. LRRC59 overexpression was correlated with infiltration of resting memory CD4 T cells, memory activated CD4 T cells, resting NK cells, macrophages M0, M1, M2, and neutrophils. IHC showed that the LRRC59 expression in BC tissue was significantly higher than that in adjacent noncancerous tissue. Knockdown of LRRC59 expression inhibited the proliferation of BC cells and reduced their migratory ability. Western blot showed that Snail and vimentin protein expressions decreased, while E‐cadherin expressions increased.ConclusionsLRRC59 expression can predict the outcome of BC independently and serve as a new biomarker for diagnosis.

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Overexpression of Karyopherin Subunit alpha 2 (KPNA2) Predicts Unfavorable Prognosis and Promotes Bladder Cancer Tumorigenicity via the P53 Pathway

Cited by 9 publications

References 44 publications

A pan-cancer analysis of the oncogenic role of Keratin 17 (KRT17) in human tumors

A pan-cancer analysis of the oncogenic role of Keratin 17 (KRT17) in human tumors

Long non-coding RNA HAGLROS facilitates tumorigenesis and progression in hepatocellular carcinoma by sponging miR-26b-5p to up-regulate karyopherin α2 (KPNA2) and inactivate p53 signaling

LRRC59 serves as a novel biomarker for predicting the progression and prognosis of bladder cancer

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