α5‐nAChR and survivin: Two potential biological targets in lung adenocarcinoma

Zhang, Yujie; Sun, Yilin; Jia, Yanfei; Zhang, Qian; Zhu, Ping

doi:10.1002/jcp.29956

Cited by 11 publications

(6 citation statements)

References 53 publications

(82 reference statements)

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“…Aberrant expression of some genes may mediate nicotine-induced carcinogenesis. For example, nicotine exposure can elevate the expression of α5 nicotinic acetylcholine receptors and survivin in lung cells, which plays an important role in the occurrence and development of lung adenocarcinoma [ 9 ]. Nicotine exposure can also induce the abnormal expression of PRX1 and the genes encoding for its interacting proteins CFL1 and PPP2R1A , thereby promoting the transformation of normal oral cells into cancer cells [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Guo

Sun

Chen

et al. 2023

Clin Exp Otorhinolaryngol

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Background: Nicotine is an ingredient of tobacco, and its exposure increases various cancer risks, including oral cancer. Previous studies have focused on its addictive properties, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process of nicotine promoting the occurrence and development of oral cancer through data mining and experimental verification. Methods: This study involved three parts. First, the key genes related to nicotine-related oral cancer were screened out through data mining; second, the expression and clinical significance of the key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.Results: SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways such as TNF and Apelin pathways; and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to Bleomycin and Docetaxel. Conclusion: This study revealed SERPINE1 as the key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.

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Section: Introductionmentioning

confidence: 99%

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Guo

Sun

Chen

et al. 2023

Clin Exp Otorhinolaryngol

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“…In addition, in the present study, BIRC5 emerged as the most significant IAP that could be developed as a marker for preventing and treating NSCLC patients. Low expression of BIRC5 mRNA was also previously positively correlated with NSCLC patient survival ( Cao et al, 2019 ; Nitschkowski et al, 2019 ; Rashed et al, 2019 ; Zhang et al, 2020b ).…”

Section: Discussionmentioning

confidence: 74%

“…Consistently, we found that BIRC5 expression levels were significantly higher in tumor tissues than in normal tissues. Previous studies have suggested BIRC5 as a predictive biomarker in NSCLC, especially for LUAD ( Zhang et al, 2020b ; Haakensen et al, 2020 ). In addition, in the present study, BIRC5 emerged as the most significant IAP that could be developed as a marker for preventing and treating NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Inhibitor of Apoptosis Protein Expression and Prognostic Significance in Non–Small Cell Lung Cancer

Lee

Huang

et al. 2021

Front. Genet.

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Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.

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“…BIRC5 is a member of the inhibitors of apoptosis (IAP) gene family, which encodes negative regulatory proteins that prevent apoptotic cell death. Unlike other IAPs, BIRC5 expresses intensely in most tumors, including LUAD and LUSC [ 55 ], and it could serve as a predictive biomarker for NSCLC, especially for LUAD [ 56 ], but does not express or only expresses at low levels in most normally differentiated tissues [ 57 ], and down-regulated BIRC5 was positively associated with NSCLC survival time [ 58 ]. Cell division cycle 6 ( CDC6 ) is an important regulator of DNA replication, and there is evidence that silencing of CDC6 may lead to G1 phase arrest [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

A Novel Strategy for Identifying NSCLC MicroRNA Biomarkers and Their Mechanism Analysis Based on a Brand-New CeRNA-Hub-FFL Network

Zhang¹,

Nie²,

Liu³

et al. 2022

IJMS

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Finding reliable miRNA markers and revealing their potential mechanisms will play an important role in the diagnosis and treatment of NSCLC. Most existing computational methods for identifying miRNA biomarkers only consider the expression variation of miRNAs or rely heavily on training sets. These deficiencies lead to high false-positive rates. The independent regulatory model is an important complement to traditional models of co-regulation and is more impervious to the dataset. In addition, previous studies of miRNA mechanisms in the development of non-small cell lung cancer (NSCLC) have mostly focused on the post-transcriptional level and did not distinguish between NSCLC subtypes. For the above problems, we improved mainly in two areas: miRNA identification based on both the NOG network and biological functions of miRNA target genes; and the construction of a 4-node directed competitive regulatory network to illustrate the mechanisms. NSCLC was classified as lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) in this work. One miRNA biomarker of LUAD (miR-708-5p) and four of LUSC (miR-183-5p, miR-140-5p, miR-766-5p, and miR-766-3p) were obtained. They were validated using literature and external datasets. The ceRNA-hub-FFL involving transcription factors (TFs), microRNAs (miRNAs), mRNAs, and long non-coding RNAs (lncRNAs) was constructed. There were multiple interactions among these components within the net at the transcriptional, post-transcriptional, and protein levels. New regulations were revealed by the network. Meanwhile, the network revealed the reasons for the previous conflicting conclusions on the roles of CD44, ACTB, and ITGB1 in NSCLC, and demonstrated the necessity of typing studies on NSCLC. The novel miRNA markers screening method and the 4-node directed competitive ceRNA-hub-FFL network constructed in this work can provide new ideas for screening tumor markers and understanding tumor development mechanisms in depth.

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α5‐nAChR and survivin: Two potential biological targets in lung adenocarcinoma

Cited by 11 publications

References 53 publications

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Comprehensive Analysis of Inhibitor of Apoptosis Protein Expression and Prognostic Significance in Non–Small Cell Lung Cancer

A Novel Strategy for Identifying NSCLC MicroRNA Biomarkers and Their Mechanism Analysis Based on a Brand-New CeRNA-Hub-FFL Network

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