Micro-ribonucleic acids (miRNAs) and a proteomic profile in lung adenocarcinoma cases with brain metastasis

Zhang, Lingling; Liang, Jianfeng; Han, Zhiyu; Wang, Lihua; Liang, Jun; Zhang, Shucai

doi:10.21037/atm-22-5703

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…At present, its pathogenesis is complex and unclear. Some studies have shown that mRNA and miRNA play important roles in the development of LUAD ( 27 , 28 ). A bioinformatics analysis showed that 4 differentially expressed miRNAs (i.e., miR-196b-5p, miR-223-3p, miR-135a-5p, and miR-9) and 4 differentially expressed mRNAs (i.e., MEIS1, HOXA5, SCARB1, and RUNX2) participate in the regulation network of the molecular mechanism of bone metastasis in LUAD ( 29 ).…”

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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“…Previous studies have identified a high-risk subtype of lung adenocarcinoma using genetic markers (1,(3)(4)(5)(6), while a study combining ribonucleic acid (RNA) and protein profiling identified pathways linked to brain metastasis in these patients (7). Abnormal expression of immune genes has been found to contribute to cancer progression (8)(9)(10), with immune factors linked to both brain metastasis and lung adenocarcinoma (11).…”

Section: Introductionmentioning

confidence: 99%

Identification of distinct tumor cell patterns with single-cell RNA sequencing integrating primary lung adenocarcinoma and brain metastasis tumor

Wang¹,

Zhang²,

Guan³

et al. 2023

Transl Lung Cancer Res

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Background: Lung adenocarcinoma (LUAD) is the most common form of lung cancer and is often accompanied by brain metastasis (BM). The heterogeneity of the tumor renders all current conventional treatments less effective. This study aims to dissect tumor cell heterogeneity and identify potential therapeutic targets.Methods: We conducted single-cell RNA-sequencing (scRNA-seq) in 8 patients with treatment-naïve LUAD BM and included scRNA-seq data of 10 primary LUAD samples and their matched adjacent normal tissue from GSE131907 to determine the tumor cell heterogeneity.Results: Our analyses revealed tumor cells derived from brain metastases were more heterogeneous. Tumor cells from BM harbored significantly more copy number variants (CNVs), and cells of magnoid subtype were the critical source of malignant cells both in BM and the primary lung tumor. Pseudo-time trajectory analysis revealed that malignant cells had upregulated genes enriched for cell cycle and cell division. Integrated analysis of tumor cells revealed 2 distinct malignant cell clusters (cluster 4 and cluster 6) and their marker genes. The signatures identified in the single-cell profile had prognostic value in the bulk tumor profiles.Moreover, the signature of cluster 4 had significant prognostic value in predicting patients surviving longer than 3.5 years, while the signature of cluster 6 showed better predictive ability within 1 year. Magnoid-type cells are most likely to develop into the riskiest cell type and potentially promote tumor progression.Conclusions: scRNA profiling that integrates LUAD BM and primary LUAD can provide information on those malignant cells with BM potential, offering additional prognostic information at cellular level, and may serve as a foundational resource for further tumor cell dissection and therapeutic target exploration.

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The role of microRNAs in brain metastasis

Hudson,

Mondia,

Zhang

et al. 2024

J Neurooncol

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Brain metastasis (BM) is the most common type of brain tumor and frequently foreshadows disease progression and poor overall survival with patients having a median survival of 6 months. 70,000 new cases of BM are diagnosed each year in the United States (US) and the incidence rate for BM is increasing with improved detection. MicroRNAs (miRNAs) are small non-coding RNAs that serve as critical regulators of gene expression and can act as powerful oncogenes and tumor suppressors. MiRNAs have been heavily implicated in cancer and proposed as biomarkers or therapeutic targets or agents. In this review, we summarize an extensive body of scientific work investigating the role of microRNAs in BM. We discuss miRNA dysregulation, functions, targets, and mechanisms of action in BM and present the current standing of miRNAs as biomarkers and potential therapeutics for BM. We conclude with future directions of miRNA basic and clinical research in BM.

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Micro-ribonucleic acids (miRNAs) and a proteomic profile in lung adenocarcinoma cases with brain metastasis

Cited by 3 publications

References 32 publications

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

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

Identification of distinct tumor cell patterns with single-cell RNA sequencing integrating primary lung adenocarcinoma and brain metastasis tumor

The role of microRNAs in brain metastasis

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