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Updated: Dec 8, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Bioinformatics analysis of differentially expressed miRNAs in non-small cell lung cancer
Hui Yu1, Zhonghao Pang1, Gang Li1
1Department of Cardiothoracic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Objective:
Non-small cell lung cancer (NSCLC) contains 85% of lung cancer. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the largest NSCLC subgroups. The aim of the study was to investigate the underlying mechanism in developing more effective subtype-specific molecular therapeutic procedures.
Methods:
A total of 876 specimens were used in this study: 494 LUAD tissues (ie, 449 LUAD tissues and 45 matched normal tissues) and 382 LUSC tissues (ie, 337 LUSC tissues and 45 matched normal tissues). The miRNA sequencing data were processed using R. The differential expressed miRNAs between lung cancer and normal tissues were analyzed using the limma package in R. Gene expression, Western blotting, hematoxylin and eosin staining, and luciferase assay were used to test LUAD and LUSC.
Results:
LUAD and LUSC appear sharply distinct at molecular and pathological level. Let-7a-5p, miR-338, miR-375, miR-217, miR-627, miR-140, miR-147b, miR-138-2, miR-584, and miR-197 are top 10 relevant miRNAs and CLDN3, DSG3, KRT17, TMEM125, KRT5, NKX2-1, KRT7, ABCC5, KRAS, and PLCG2 are top 10 relevant genes in NSCLC. At the same time, the miRNAs expression levels were also quite different between the two groups. Among the differential expressed miRNAs, let-7a-5p was significantly down-regulated in LUAD while miR-338 was markedly down-regulated in LUSC. Bioinformatics analyses appeared that let-7a-5p directly targets high-molecular weight keratin 5 (KRT5) which were shown to be a strong risk factor for LUAD. And NK2 homeobox 1(NKX2-1) which was associated with tumor progression in LUSC was identified as a target gene of miR-338.
Conclusions:
Distinct profile of miRNAs can take a part in the development of LUAD and LUSC and thus could serve as a subtype-specific molecular therapeutic target to protect against LUAD and LUSC.
Insights
MicroRNA profiles differ significantly between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). These distinct microRNAs offer potential as subtype-specific therapeutic targets for non-small cell lung cancer (NSCLC).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases.
- Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the predominant NSCLC subtypes.
- Developing subtype-specific molecular therapies is crucial for improving treatment efficacy.
Purpose of the Study:
- To investigate the distinct molecular mechanisms underlying LUAD and LUSC development.
- To identify potential subtype-specific molecular therapeutic targets for NSCLC.
Main Methods:
- Analysis of miRNA sequencing data from 876 lung cancer and normal tissue specimens.
- Differential expression analysis of miRNAs using the limma package in R.
- Validation through gene expression analysis, Western blotting, and luciferase assays.
Main Results:
- LUAD and LUSC exhibit distinct molecular and pathological profiles.
- Top relevant miRNAs include let-7a-5p and miR-338, with let-7a-5p down-regulated in LUAD and miR-338 in LUSC.
- let-7a-5p targets KRT5 (a LUAD risk factor), and miR-338 targets NKX2-1 (associated with LUSC progression).
Conclusions:
- Distinct microRNA (miRNA) profiles are implicated in the pathogenesis of LUAD and LUSC.
- These specific miRNA signatures represent promising targets for subtype-specific molecular therapies.
- Targeting these miRNAs could lead to more effective treatments for LUAD and LUSC.
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MicroRNAs
MicroRNAs
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