RBBP4 Enhances Platinum Chemo Resistance in Lung Adenocarcinoma

Wang, Nianwu; Wang, Wei; Mao, Wenli; Kuerbantayi, Nazuke; Jia, Ning; Chen, Yan; Zhou, Fang; Li, Yin; Wang, Yukun

doi:10.1155/2021/6905985

Cited by 7 publications

(4 citation statements)

References 26 publications

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“…RBBP4 plays a crucial role in various types of cancers. Dysregulated expression of RBBP4 is associated with metastasis and unfavorable prognosis in highly aggressive and metastatic cancers, such as non-small cell lung cancer cells ( Wang et al, 2021 ; Cao et al, 2021 ). Tumorigenesis is also suppressed following the inhibition of RBBP4 expression.…”

Section: Discussionmentioning

confidence: 99%

Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4

Jia,

Shen,

Wei

et al. 2023

PeerJ

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Background Ropivacaine is a local anesthetic commonly used in regional nerve blocks to manage perioperative pain during lung cancer surgery. Recently, the antitumor potential of ropivacaine has received considerable attention. Our previous study showed that ropivacaine treatment inhibits the malignant behavior of lung cancer cells in vitro. However, the potential targets of ropivacaine in lung cancer cells have not yet been fully identified. This study aimed to explore the antitumor effects and mechanisms of action of ropivacaine in lung cancer. Methods Lung cancer A549 cells were treated with or without 1 mM ropivacaine for 48 h. Quantitative proteomics was performed to identify the differentially expressed proteins (DEPs) triggered by ropivacaine treatment. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and analyze the most significant hub genes. Overexpression plasmids and small interfering RNA were used to modulate the expression of key DEPs in A549 and H1299 cells. MTS, transwell assays, and flow cytometry were performed to determine whether the key DEPs were closely related to the anticancer effect of ropivacaine on the malignant behavior of A549 and H1299 cells. Results Quantitative proteomic analysis identified 327 DEPs (185 upregulated and 142 downregulated proteins) following ropivacaine treatment. Retinoblastoma-binding protein 4 (RBBP4) was one of the downregulated DEPs and was selected as the hub protein. TCGA database showed that RBBP4 was significantly upregulated in lung cancer and was associated with poor patient prognosis. Inhibition of RBBP4 by siRNA resulted in a significant decrease in the proliferation and invasive capacity of lung cancer cells and the induction of cell cycle arrest. Additionally, the results indicated RBBP4 knockdown enhanced antitumor effect of ropivacaine on A549 and H1299 cells. Conversely, the overexpression of RBBP4 using plasmids reversed the inhibitory effects of ropivacaine. Conclusion Our data suggest that ropivacaine suppresses lung cancer cell malignancy by downregulating RBBP4 protein expression, which may help clarify the mechanisms underlying the antitumor effects of ropivacaine.

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Section: Discussionmentioning

confidence: 99%

Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4

Jia,

Shen,

Wei

et al. 2023

PeerJ

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“…And the correlation between MEs and clinical traits (diagnosed sepsis or healthy) was computed. Then the gene-trait significance value (GS), which represented the relative level between genes and traits, were calculated by the value of Pearson’s correlation in order to identify genes most associated with sepsis [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

ARG1 as a promising biomarker for sepsis diagnosis and prognosis: evidence from WGCNA and PPI network

Zhang

Xing

et al. 2022

Hereditas

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Background Sepsis is a life-threatening multi-organ dysfunction caused by the dysregulated host response to infection. Sepsis remains a major global concern with high mortality and morbidity, while management of sepsis patients relies heavily on early recognition and rapid stratification. This study aims to identify the crucial genes and biomarkers for sepsis which could guide clinicians to make rapid diagnosis and prognostication. Methods Preliminary analysis of multiple global datasets, including 170 samples from patients with sepsis and 110 healthy control samples, revealed common differentially expressed genes (DEGs) in peripheral blood of patients with sepsis. After Gene Oncology (GO) and pathway analysis, the Weighted Gene Correlation Network Analysis (WGCNA) was used to screen for genes most related with clinical diagnosis. Also, the Protein-Protein Interaction Network (PPI Network) was constructed based on the DEGs and the hub genes were found. The results of WGCNA and PPI network were compared and one shared gene was discovered. Then more datasets of 728 experimental samples and 355 control samples were used to prove the diagnostic and prognostic value of this gene. Last, we used real-time PCR to confirm the bioinformatic results. Results Four hundred forty-four common differentially expressed genes in the blood of sepsis patients from different ethnicities were identified. Fifteen genes most related with clinical diagnosis were found by WGCNA, and 24 hub genes with most node degrees were identified by PPI network. ARG1 turned out to be the unique overlapped gene. Further analysis using more datasets showed that ARG1 was not only sharply up-regulated in sepsis than in healthy controls, but also significantly high-expressed in septic shock than in non-septic shock, significantly high-expressed in severe or lethal sepsis than in uncomplicated sepsis, and significantly high-expressed in non-responders than in responders upon early treatment. These all demonstrate the performance of ARG1 as a key biomarker. Last, the up-regulation of ARG1 in the blood was confirmed experimentally. Conclusions We identified crucial genes that may play significant roles in sepsis by WGCNA and PPI network. ARG1 was the only overlapped gene in both results and could be used to make an accurate diagnosis, discriminate the severity and predict the treatment response of sepsis.

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“…Elevated RBBP4 expression in non-small cell LC (NSCLC) tissues amplifies cell proliferation and invasion, and is concomitantly linked to an adverse clinical outcome ( 13 , 84 ). RBBP4 is also increased in cisplatin-resistant NSCLC, affecting drug resistance ( 85 ), and is associated with enhanced DNA damage sensitivity and repair pathway activity ( 86 ). Additionally, in lung adenocarcinoma (LUAD) cells, RBBP4 interacts with chromobox homolog 3, which is found to be upregulated in current smokers with LUAD, thereby promoting LUAD progression ( 87 ).…”

Section: Expression and Function Of Rbbp4/7 In Diseasesmentioning

confidence: 99%

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)

Zhan,

Yin,

et al. 2024

Int J Mol Med

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Histone chaperones serve a pivotal role in maintaining human physiological processes. They interact with histones in a stable manner, ensuring the accurate and efficient execution of DNA replication, repair and transcription. Retinoblastoma binding protein (RBBP)4 and RBBP7 represent a crucial pair of histone chaperones, which not only govern the molecular behavior of histones H3 and H4, but also participate in the functions of several protein complexes, such as polycomb repressive complex 2 and nucleosome remodeling and deacetylase, thereby regulating the cell cycle, histone modifications, DNA damage and cell fate. A strong association has been indicated between RBBP4/7 and some major human diseases, such as cancer, age-related memory loss and infectious diseases. The present review assesses the molecular mechanisms of RBBP4/7 in regulating cellular biological processes, and focuses on the variations in RBBP4/7 expression and their potential mechanisms in various human diseases, thus providing new insights for their diagnosis and treatment.

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RBBP4 Enhances Platinum Chemo Resistance in Lung Adenocarcinoma

Cited by 7 publications

References 26 publications

Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4

Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4

ARG1 as a promising biomarker for sepsis diagnosis and prognosis: evidence from WGCNA and PPI network

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review)

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