Identification of a panel of mitotic spindle‐related genes as a signature predicting survival in lung adenocarcinoma

Zhang, Liwen; He, Miao; Zhu, Wenjing; Lv, Xuemei; Zhao, Yimeng; Yan, Yuanyuan; Li, Xueping; Jiang, Longyang; Zhao, Lin; Fan, Yue; Su, Panpan; Gao, Mengcong; Ma, Heyao; Li, Kai

doi:10.1002/jcp.29312

Cited by 23 publications

(18 citation statements)

References 41 publications

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“…Previous research has confirmed that BUB1 could be viewed as a clinical biomarker for adverse prognosis and a potential therapeutic target in various tumours, 15,16 including aggressive colorectal cancer, 17 breast cancer 18 and glioblastoma 19 . Consistent with these studies, we showed that the overexpression of the BUB1 protein was associated with a poor response to chemotherapy and distant metastasis of OS.…”

Section: Discussionsupporting

confidence: 89%

Inhibition of BUB1 suppresses tumorigenesis of osteosarcoma via blocking of PI3K/Akt and ERK pathways

Huang

Wang

Wei

et al. 2021

J Cellular Molecular Medi

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Osteosarcoma (OS) is a primary malignant bone tumour that mainly affects teenagers, with patients displaying poor prognosis. Budding uninhibited by benzimidazoles 1 (BUB1), a type of serine/threonine kinase that is linked to pro‐tumorigenic phenomena, has not been well studied in OS. Hence, this study aimed to explore the role of BUB1 in OS. The expression of BUB1 in OS specimens and cell lines was assessed using immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were applied to evaluate the impact of BUB1 on patient survival. Cell counting kit‐8, wound‐healing and Transwell assays, as well as flow cytometry, were used to investigate the influence of BUB1 inhibition on OS in vitro. Moreover, a tumour xenograft model was established to investigate the in vivo effect of BUB1 inhibition on OS tumour growth. Results showed that BUB1 was overexpressed in OS specimens and cell lines. Furthermore, BUB1 overexpression was closely associated with the poor clinical outcomes of patients with OS. Inhibition of BUB1 markedly suppressed cell proliferation and tumour growth, cell migration, invasion and induced cell apoptosis of OS by blocking the PI3K/Akt and ERK signalling pathways. Thus, our study suggested that overexpression of BUB1 protein contributed to poor survival of OS patients and that inhibition of BUB1 resulted in considerable anti‐tumour activity associated with proliferation, migration, invasion and apoptosis of OS.

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Section: Discussionsupporting

confidence: 89%

Inhibition of BUB1 suppresses tumorigenesis of osteosarcoma via blocking of PI3K/Akt and ERK pathways

Huang

Wang

Wei

et al. 2021

J Cellular Molecular Medi

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“…Although BUB1 seems to be a tumor suppressor, enhanced BUB1 expression causes chromosome instability and further induced oncogenesis [62]. Similar to CCNB2, BUB1 is also a hub protein in the NSCLC protein-protein interaction network and its overexpression is a poor prognostic indicator for NSCLC patients [59,63]. BUB1 inhibitors, in combination with taxanes or PARP inhibitors, could improve treatment efficacy and potentially overcome drug resistance [64].…”

Section: Discussionmentioning

confidence: 99%

HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas

Sun

Zhang

et al. 2021

Genes

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We previously demonstrated that proline-rich protein 11 (PRR11) and spindle and kinetochore associated 2 (SKA2) constituted a head-to-head gene pair driven by a prototypical bidirectional promoter. This gene pair synergistically promoted the development of non-small cell lung cancer. However, the signaling pathways leading to the ectopic expression of this gene pair remains obscure. In the present study, we first analyzed the lung squamous cell carcinoma (LSCC) relevant RNA sequencing data from The Cancer Genome Atlas (TCGA) database using the correlation analysis of gene expression and gene set enrichment analysis (GSEA), which revealed that the PRR11-SKA2 correlated gene list highly resembled the Hedgehog (Hh) pathway activation-related gene set. Subsequently, GLI1/2 inhibitor GANT-61 or GLI1/2-siRNA inhibited the Hh pathway of LSCC cells, concomitantly decreasing the expression levels of PRR11 and SKA2. Furthermore, the mRNA expression profile of LSCC cells treated with GANT-61 was detected using RNA sequencing, displaying 397 differentially expressed genes (203 upregulated genes and 194 downregulated genes). Out of them, one gene set, including BIRC5, NCAPG, CCNB2, and BUB1, was involved in cell division and interacted with both PRR11 and SKA2. These genes were verified as the downregulated genes via RT-PCR and their high expression significantly correlated with the shorter overall survival of LSCC patients. Taken together, our results indicate that GLI1/2 mediates the expression of the PRR11-SKA2-centric gene set that serves as an unfavorable prognostic indicator for LSCC patients, potentializing new combinatorial diagnostic and therapeutic strategies in LSCC.

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“…BUB1, BUB1B, PLK1, and CDC20 were suggested as LUAD stem cell biomarkers (60). CENPF, KIF2C, CDK1, ASPM, and MYH10 were also proposed as diagnosis and prognosis biomarkers of LUAD (61)(62)(63)(64)(65)(66). CDKN3 was not yet reported as a diagnosis or prognosis biomarker but expected to be a promising therapeutic target in LUAD (63).…”

Section: Discussionmentioning

confidence: 99%

A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma

et al. 2021

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Lung adenocarcinoma (LUAD) is one of the most common and malignant cancer types. Abnormal cell proliferation, exemplified by cell cycle and cell division dysregulation, is one of the most prominent hallmarks of cancer and is responsible for recurrence, metastasis, and resistance to cancer therapy. However, LUAD-specific gene regulation and clinical significance remain obscure. Here, by using both tissues and cells from LUAD and normal lung samples, 434 increased and 828 decreased genes of biological significance were detected, including 127 cell cycle-associated genes (95 increased and 32 decreased), 66 cell division-associated genes (56 increased and 10 decreased), and 81 cell proliferation-associated genes (34 increased and 47 decreased). Among them, 12 increased genes (TPX2, CENPF, BUB1, PLK1, KIF2C, AURKB, CDKN3, BUB1B, HMGA2, CDK1, ASPM, and CKS1B) and 2 decreased genes (TACC1 and MYH10) were associated with all the three above processes. Importantly, 2 (CDKN3 and CKS1B) out of the 11 increased genes (except HMGA2) are previously uncharacterized ones in LUAD and can potentially be prognostic markers. Moreover, PLK1 could be a promising therapeutic target for LUAD. Besides, protein–protein interaction network analysis showed that CDK1 and CDC20 were the hub genes, which might play crucial roles in cell proliferation of LUAD. Furthermore, transcriptional regulatory network analysis suggested that the transcription factor E2F1 could be a key regulator in controlling cell proliferation of LUAD via expression modulation of most cell cycle-, cell division-, and cell proliferation-related DEGs. Finally, trichostatin A, hycanthone, vorinostat, and mebeverine were identified as four potential therapeutic agents for LUAD. This work revealed key regulators contributing to cell proliferation in human LUAD and identified four potential therapeutic agents for treatment strategy.

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Identification of a panel of mitotic spindle‐related genes as a signature predicting survival in lung adenocarcinoma

Abstract: Lung adenocarcinoma (LUAD) is one of the most malignant tumor types worldwide.

Cited by 23 publications

References 41 publications

Inhibition of BUB1 suppresses tumorigenesis of osteosarcoma via blocking of PI3K/Akt and ERK pathways

Inhibition of BUB1 suppresses tumorigenesis of osteosarcoma via blocking of PI3K/Akt and ERK pathways

HEDGEHOG/GLI Modulates the PRR11-SKA2 Bidirectional Transcription Unit in Lung Squamous Cell Carcinomas

A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma

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