Uronic acid pathway metabolites regulate mesenchymal transition and invasiveness in lung adenocarcinoma

Zhao, Yingxin; Brasier, Allan R.

doi:10.21037/biotarget.2019.09.01

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…LUAD is a malignant tumor, has shown the fastest increase in incidence and mortality rates, and thus represents a great threat to human health and life ( 10 ). At present, its pathogenesis is complex and unclear.…”

Section: Discussionmentioning

confidence: 99%

Identification of the key miRNA-mRNA regulatory network in lung adenocarcinoma

Xue¹,

You²,

Liu³

et al. 2023

J Thorac Dis

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Background Lung adenocarcinoma (LUAD) is the most common type of lung cancer, has a high incidence rate and is a serious threat to human health. However, the pathogenesis of LUAD is still unclear. Further research on the pathogenesis of LUAD may provide targets for the early diagnosis and treatment of LUAD. Methods First, a transcriptome analysis was conducted to sequence the messenger RNA (mRNA) and micro RNA (miRNA) of the LUAD and adjacent control tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then performed for the functional annotation. Next, a differential miRNA-differential mRNA regulatory network was then constructed, and the function of the mRNAs in the network was analyzed and the key regulatory molecules (the hub molecules) were identified. Cytohubba was then used to analyze the top 20 hub molecules in the total miRNA-mRNA network, and the miRNAs regulating the top 20 hub genes (of which 2 were upregulated and 18 were downregulated). Finally, the key molecules were identified. Results By analyzing the function of the mRNA molecules in the regulatory network, we found that the immune response was inhibited, as were the movement and adhesion of immune-related cells; however, cell tumorigenesis, body death, and tumor cell proliferation were activated. The functions of the 20 hub molecules were mainly related to cytotoxicity, cell exosmosis, and cell adhesion mediated by immune cells. Further, we found that miR-5698, miR224-5p, and miR4709-3P regulate multiple key genes (e.g., PECAM1 , CX3CR1 , KLRD1 , and CXCL12 ), and may be the key miRNAs regulating LUAD. Conclusions Immune response, cell tumorigenesis, and tumor cell proliferation play central roles in the overall regulatory network. miR-5698, miR224-5p, and miR4709-3p may be important biomarkers for the occurrence and development of LUAD and have great potential in the prognosis of LUAD patients and the development of new therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification of the key miRNA-mRNA regulatory network in lung adenocarcinoma

Xue¹,

You²,

Liu³

et al. 2023

J Thorac Dis

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show abstract

“…Although there have been considerable advancements in treatment strategies for LUAD, the overall short-term survival of NSCLC patients has not exceeded 20% in the past few decades ( 3 ). Increasing evidence indicates that malignant proliferation and distant metastasis are the main challenges of cancer treatment ( 7 ). Therefore, studying the genes associated with tumor metastasis in the pathophysiological process of LUAD is crucial, and targeting these genes may be a potential approach for the treatment of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2

Cao¹,

Xue²,

Chen³

et al. 2022

Ann Transl Med

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Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis is still unclear. The present study aimed to investigate the role of miR-202-3p and its downstream target gene, ribonucleotide reductase regulatory subunit M2 (RRM2), in the occurrence and development of LUAD and elucidate the correlation between RRM2 and the clinicopathological stage and prognosis of LUAD. Methods:The expression of miR-202-3p was analyzed using the CancerMIRNome database and quantitative polymerase chain reaction (qPCR). The effects of miR-202-3p and RRM2 on the proliferation, migration, and invasion of A549 cells were analyzed. A dual luciferase reporter assay was used to verify the targeting of miR-202-3p and RRM2. Additionally, the correlation between RRM2 expression and clinicopathology was analyzed. Results: (I) MiR-202-3p was lowly expressed in LUAD and the LUAD cell lines. qPCR confirmed that microRNA (miRNA) transfection was effective and sufficient for subsequent experiments. (II) MiR-202-3p inhibited the proliferation, invasion, and migration of LUAD cells. (III) There was a targeting relationship between miR-202-3p and RRM2, and miR-202-3p affected the expression of the RRM2 protein. RRM2 was highly expressed in lung cancer tissue. (IV) RRM2 was associated with the clinicopathological staging of lung cancer. The prognosis of patients with low RRM2 expression was better, and the prognostic sensitivity of RRM2 to lung cancer was high. RRM2 may exert its effects via the Notch pathway. (V) Si-RRM2 inhibited the expression of the RRM2 protein. RRM2 promoted the proliferation, migration, and invasion of LUAD cells. A miR-202-3p inhibitor restored the inhibitory effect of si-RRM2 on LUAD cells. Conclusions: MiR-202-3p was lowly expressed in lung cancer tissue. MiR-202-3p overexpression inhibited the proliferation and metastasis of lung cancer cells. RRM2 was highly expressed in lung cancer tissue and promoted the proliferation and metastasis of lung cancer cells. MiR-202-3p targeted and inhibited RRM2, thereby reducing the proliferation and metastasis of LUAD cells. LUAD patients with low RRM2 expression had a better prognosis, and the expression level of RRM2 was correlated with the clinical characteristics of lung cancer patients.

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“…In recent years, the role of different lung cancer-related genes in lung cancer has not been widely explored. However, experimental evidence has shown that many lung cancer-related genes are involved in the pathogenesis and development of tumors (7). For example, in acute myeloid leukemia (AML), core-binding factor subunit alpha 2 to translocation 3 can inhibit retinoic acid receptors in many AML subtypes and patient samples.…”

Section: Introductionmentioning

confidence: 99%

The predictive prognostic values of CBFA2T3, STX3, DENR, EGLN1, FUT4, and PCDH7 in lung cancer

et al. 2021

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Background: Lung cancer is one of the most malignant tumors. However, neither the pathogenesis of lung cancer nor the prognosis markers are completely clear. The purpose of this study is to screen the diagnostic or prognostic markers of lung cancer.Methods: TCGA and GEO datasets were used to analyze the relationship between lung cancer-related genes and lung cancer samples. Common differential genes were screened, and a univariate Cox regression analysis was used to screen survival related genes. A univariable Cox proportional hazards regression analysis was used to verify the genes and construct risk model. The key factors affecting the prognosis of lung cancer were determined by univariate and multivariate regression analyses. The ROC curve, AUC and the survival of each risk gene was analyzed. Finally, the biological functions of high-and low-risk patients were explored by GSEA and an immune-infiltration analysis.Results: Based on the common differential genes, 13 genes significantly related to lung cancer survival were identified. Eight risk genes (CBFA2T3, DENR, EGLN1, FUT2, FUT4, PCDH7, PHF14, and STX3) were screened out. The results showed that risk status may be an independent prognostic factor, and the risk score predicted the prognosis of lung cancer. CBFA2T3 and STX3 are protective genes, while DENR, EGLN1, FUT4 and PCDH7 are dangerous genes. These 6 genes can be used as independent lung cancer prognosis markers. The corresponding biological functions of genes expressed in high-risk patients were mostly related to tumor proliferation and inflammatory infiltration. Neutrophil, CD8 + T, Macrophage M0, Macrophage M1-and mDC-activated cells were high in high-risk status samples.Conclusions: CBFA2T3, STX3, DENR, EGLN1, FUT4, and PCDH7 are important participants in the occurrence and development of lung cancer. High-risk patients display serious inflammatory infiltration.This study not only provides insight into the mechanism of occurrence and development of lung cancer, but also provides potential targets for targeted therapy of lung cancer.

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Uronic acid pathway metabolites regulate mesenchymal transition and invasiveness in lung adenocarcinoma

Cited by 4 publications

References 25 publications

Identification of the key miRNA-mRNA regulatory network in lung adenocarcinoma

Identification of the key miRNA-mRNA regulatory network in lung adenocarcinoma

MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2

The predictive prognostic values of CBFA2T3, STX3, DENR, EGLN1, FUT4, and PCDH7 in lung cancer

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