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Published on: March 30, 2019
Influence of miR-7a and miR-24-3p on the SOX18 transcript in lung adenocarcinoma
Mateusz Olbromski1, Adam Rzechonek2, Jedrzej Grzegrzolka1
1Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
Abstract:
The molecular pathogenesis of the development of non-small cell lung carcinomas (NSCLCs) is extremely complex. Understanding the molecular basis of the development of this malignant tumor may enable the use of targeted therapy, which may result in a better treatment outome for these patients. Adenocarcinoma (AC) is the most common NSCLC subtype, equally common among smokers and non-smokers, and its pathogenesis remains unknown. The SOX18 protein is an important protein that plays a role in the development of blood and lymphatic vessels during the process of embryogenesis. Recent studies have also shown that the SOX18 protein may play a significant role in tumors, including lung cancers. In the present study, we analyzed the expression of the SOX18 protein and the mRNA level in postoperative samples of AC and non-malignant lung tissues (NMLTs), and a disparity in both levels was observed. Based on our previous observations that miR-7a and miR-24-3p are able to modulate SOX18 expression in NSCLC, the main aim of this study was to verify the miRNA modulation of the SOX18 transcript with the use of the MirTrap System in established lung cancer cell lines NCI-H1703, NCI-H522 and A549. The SOX18 mRNA expression level was significantly lower in AC than that noted in the NMLTs (P<0.0001). However, the protein levels were higher in AC cases compared to levels noted in the NMLTs (P<0.0001). Additionally, correlations between the RQ values of SOX18 in NMLT and AC cases (r=0.8195, P=0.0001), and between miR-7a and miR24-3p in AC cases (r=0.4344, P=0.0016), were noted. In conclusion, we confirmed that miR-7a and miR-24-3p are more highly expressed in NMLTs than in the AC samples, and that they modulate the SOX18 transcript in NSCLC cells.
Insights
This study reveals that microRNAs miR-7a and miR-24-3p are highly expressed in non-malignant lung tissues compared to non-small cell lung cancer (NSCLC) adenocarcinoma. These microRNAs modulate SOX18 expression, offering potential therapeutic targets for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Non-small cell lung carcinoma (NSCLC) pathogenesis is complex, with adenocarcinoma (AC) being the most common subtype.
- SOX18 protein, crucial for embryogenesis, is implicated in tumor development, including lung cancers.
- Understanding molecular drivers of AC may lead to targeted therapies.
Purpose of the Study:
- To analyze SOX18 protein and mRNA expression in AC versus non-malignant lung tissues (NMLTs).
- To investigate the modulation of SOX18 by miR-7a and miR-24-3p in NSCLC cell lines.
- To confirm the role of specific microRNAs in regulating SOX18 in lung cancer.
Main Methods:
- Analysis of SOX18 protein and mRNA levels in postoperative AC and NMLT samples.
- Utilizing the MirTrap System to study miRNA modulation of SOX18 in NCI-H1703, NCI-H522, and A549 lung cancer cell lines.
- Correlation analysis of SOX18 expression and microRNA levels.
Main Results:
- SOX18 mRNA levels were significantly lower in AC compared to NMLTs (P<0.0001).
- SOX18 protein levels were significantly higher in AC compared to NMLTs (P<0.0001).
- miR-7a and miR-24-3p were more highly expressed in NMLTs than in AC samples and modulate SOX18 transcript.
Conclusions:
- SOX18 exhibits differential expression at mRNA and protein levels in lung adenocarcinoma.
- miR-7a and miR-24-3p play a regulatory role in SOX18 expression within NSCLC.
- These findings highlight potential microRNA-based therapeutic strategies for lung adenocarcinoma.
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