Nonnegative matrix factorization‐based bioinformatics analysis reveals that TPX2 and SELENBP1 are two predictors of the inner sub‐consensuses of lung adenocarcinoma

Wang, Haiwei; Wang, Xinrui; Xu, Liangpu; Cao, Hua; Zhang, Ji

doi:10.1002/cam4.4386

Cited by 8 publications

(10 citation statements)

References 71 publications

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“…Our and previous results suggest that non-negative matrix factorization (NMF) is a robust clustering method in colon cancer 27 , 28 , liver cancer 29 , lung cancer 30 and lower grade glioma 31 . Here, using NMF algorithm, VHL mutant ccRCC from TCGA 7 and E-MTAB-1980 32 datasets was divided into two sub-clusters.…”

Section: Introductionmentioning

confidence: 64%

PBX1, EMCN and ERG are associated with the sub-clusters and the prognosis of VHL mutant clear cell renal cell carcinoma

Wang

et al. 2022

Sci Rep

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The molecular heterogeneity of primary clear cell renal cell carcinoma (ccRCC) has been reported. However, the classifications of Von Hippel–Lindau (VHL) mutant ccRCC are unclear. Here, VHL mutant ccRCC from The Cancer Genome Atlas and E-MTAB-1980 datasets were divided into two sub-clusters through non-negative matrix factorization algorithm. Most VHL mutant ccRCC patients in sub-cluster2 were with pathological T1 stage and VHL mutant ccRCC patients in sub-cluster1 were with decreased overall survival. DNA replication and homologous recombination scores were higher, while, WNT signaling pathway and regulation of autophagy scores were lower in sub-cluster1 VHL mutant ccRCC. Moreover, PBX1 transcriptional scores and mRNA expressions were lower in sub-cluster1 VHL mutant ccRCC patients and were associated with the overall survival of VHL mutant ccRCC. Furthermore, PBX1 associated genes EMCN and ERG were down-regulated in sub-cluster1 VHL mutant ccRCC and overall survival was decreased in EMCN or ERG lowly expressed VHL mutant ccRCC patients. Also, PBX1 and EMCN were down-regulated in ccRCC tissues, compared with normal kidney tissues. At last, we constructed risk models based on PBX1, EMCN and EGR expression features. With the increase of the risk score, the number of death of VHL mutant ccRCC patients was increased.

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Section: Introductionmentioning

confidence: 64%

PBX1, EMCN and ERG are associated with the sub-clusters and the prognosis of VHL mutant clear cell renal cell carcinoma

Wang

et al. 2022

Sci Rep

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“…TPX2 is a spindle assembly factor required for the normal assembly of mitotic spindles, and TPX2 is frequently reported to be considerably increased in various cancers 52–54 . Elevated TPX2 expression shows a positive correlation with tumor grade, stage, lymph node metastasis, recurrence, and poor patient survival 53,55 . The TPX2/Aurora A kinase heterodimer complex orchestrates mitotic spindle events to maintain genome integrity.…”

Section: Discussionmentioning

confidence: 99%

“…[52][53][54] Elevated TPX2 expression shows a positive correlation with tumor grade, stage, lymph node metastasis, recurrence, and poor patient survival. 53,55 The TPX2/Aurora A kinase heterodimer complex orchestrates mitotic spindle events to maintain genome integrity. Moreover, it counteracts 53BP1 chromatin accumulation to ensure genomic stability.…”

Section: Discussionmentioning

confidence: 99%

KIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation

Zhang

Zhao

et al. 2022

Molecular Carcinogenesis

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BackgroundKinesin family member 4A (KIF4A) belongs to the kinesin superfamily proteins, which are closely associated with mitophagy. However, the role of KIF4A in endometrial cancer (EC) remains poorly characterized. Here, we aimed to explore the function and regulatory mechanisms of KIF4A in EC. MethodsThe expression of KIF4A was evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemistry. Cell proliferation was measured using Cell Counting Kit-8, clone formation, and 5ethynyl-2′-deoxyuridine staining assays. Flow cytometry was performed using annexin V/propidium iodide (PI) to identify apoptotic cells and PI staining to analyze the cell cycle. RNA-seq, coimmunoprecipitation, immuno uorescence, and western blotting were performed to explore the underlying mechanism. ResultsIn this study, we demonstrated that KIF4A was upregulated and predicted a poor prognosis in patients with EC. KIF4A knockdown in EC cells resulted in attenuated proliferative capacity and promoted cell cycle arrest and apoptosis induced by increased DNA damage. Mechanistic investigations indicated that KIF4A knockdown exacerbated DNA damage repair and response by regulating the stability of the spindle assembly factor TPX2. ConclusionsKIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation. KIF4A may serve as a promising therapeutic target for endometrial cancer molecular mechanism of EC progression and identify novel diagnostic markers and therapeutic targets for patients with EC. Kinesins are microtubule-based motor proteins that mediate diverse functions within the cell, including the transport of vesicles, organelles, chromosomes, and protein complexes and the movement of microtubules [8,9]. Individual kinesin family members have speci c functions. Some kinesins are involved in axonal transport, whereas others function exclusively during mitosis [10]. To date, 45 kinesin superfamily proteins (KIFs) with varying functions have been discovered in humans [11], and at least 12 of them are required in various aspects of mitosis, including bipolar spindle assembly, chromosome alignment, chromosome segregation, and cytokinesis [12,13]. Multiple kinesins also promote the proliferation and progression of pancreatic cancer[14], hepatocellular carcinoma [15][16][17], glioblastoma [18,19], melanoma [20,21], and lung adenocarcinoma [22]. KIFC1 and KIF2C are upregulated and accelerate the proliferation of EC [23,24]. However, the role of kinesins in EC has not yet been fully investigated.In the present study, to evaluate the role of kinesins in EC, we analyzed differentially expressed kinesins in The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) and GSE17025 databases and found that kinesin family member 4A (KIF4A) was most prominently upregulated. Furthermore, we demonstrated that KIF4A accelerated EC progression by regulating cell proliferation and division by inhibiting the apoptosis of EC cells. Mechanistic investigations demonstr...

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“…8,9 It has been suggested that TPX2 could be used as a marker for poor prognosis in lung adenocarcinoma (LUAD) by data analysis. [15][16][17] TPX2 overexpression also caused resistance to EGFR TKI and radiation in NSCLC. 18 So, understanding the mechanism of TPX2 has become an important issue.…”

Section: Introductionmentioning

confidence: 99%

Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel

Hu¹,

He²,

Tian³

et al. 2023

OTT

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Background: Lung cancer, most of which is non-small cell lung cancer (NSCLC), is the most common tumor in the world, and drug resistance, as a major problem in clinical treatment, has attracted extensive attention. However, the role and mechanism of Targeting protein for Xenopus kinesin-like protein 2 (TPX2), which is highly expressed in NSCLC, is still unclear. Methods: Bioinformatics analysis was used to analyze the relationship between TPX2 and the clinicopathological features of NSCLC. Stable TPX2 overexpression cell lines with were constructed by lentivirus infection, and the effect of TPX2 on proliferation, migration, invasion and chemoresistance to docetaxel was characterized by the CCK8, wound healing, transwell, colony formation assay and FACS. An in vivo lung homing mouse model was used to further confirmed the role of TPX2 on metastasis. Exosomes were extracted by differential centrifugation from the culture supernatant, and their functions were investigated by co-culture with tumor cells. Gene expression was detected via Western blot and real time PCR (RT-qPCR). Results: Overexpression of TPX2 was related to the poor prognosis of NSCLC. Promoted migration, invasion and metastasis, and reduced the sensitivity of NSCLC cells to docetaxel. The abundance of TPX2 can be packaged in vesicles and transported to other cells. In addition, overexpression of TPX2 induced the accumulation of β-catenin and C-myc. Conclusion: Our findings indicated that intercellular transfer of exosomal TPX2 triggered metastasis and resistance against to docetaxel in lung cancer cells, through activating downstream WNT/β-catenin signaling pathway.

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Nonnegative matrix factorization‐based bioinformatics analysis reveals that TPX2 and SELENBP1 are two predictors of the inner sub‐consensuses of lung adenocarcinoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 8 publications

References 71 publications

PBX1, EMCN and ERG are associated with the sub-clusters and the prognosis of VHL mutant clear cell renal cell carcinoma

PBX1, EMCN and ERG are associated with the sub-clusters and the prognosis of VHL mutant clear cell renal cell carcinoma

KIF4A promotes genomic stability and progression of endometrial cancer through regulation of TPX2 protein degradation

Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel

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