Two lung development-related microRNAs, miR-134 and miR-187, are differentially expressed in lung tumors

Abstract

Introduction: MicroRNAs (miRNAs) are involved in various cellular events needed for embryonic development and tumorigenesis. As some of the development-specific gene expression patterns could be observed in cancers, we speculated that the expression pattern of lung development-specific miRNAs miR-134 and miR-187 might be altered in lung tumor samples. Lung cancer is the first cause of cancer related deaths worldwide, mostly due to its late diagnosis. Therefore, finding a reliable diagnostic tumor marker, based on molecular profile of tumorigenesis, would be critical in lowering lung cancer mortality.

Methods: We employed a real-time RT-PCR approach to evaluate the expression alteration of two lung development-related miRNAs in lung tumor tissues. The suitability of miRs expression alterations as lung tumor biomarkers was tested by receiver operating characteristic (ROC) curve analysis. The effect of miR-187 overexpression on a lung carcinoma cell cycle was assessed using flow cytometry analysis.

Results: Our data revealed a significant upregulation (7.8 times, p<0.02) of miR-134 in lung tumors. However, its expression level failed to discriminate different tumor types and grades of malignancies from each other. Moreover, the ROC curves analysis did not give it a good score as a reliable biomarker (AUC=0.522, P=0.729). In contrast, miR-187 showed a significant down-regulation (P=0.008) in lung tumors. Similarly, its expression level failed to differentiate different tumor types or grades of malignancies. Nevertheless, ROC curve analysis gave it an AUC score of 0.669 (P=0.012), which suggests its suitability as a potential biomarker for lung cancer. Furthermore, ectopic expression of miR-187 in A549 cells caused a cell cycle arrest in G1 phase (P=0.013).

Conclusion: Altogether, our data demonstrated an altered expression of two development-related miRNAs namely miR-134 and miR-187 in lung tumors for the first time. Moreover we have shown that miR-134 and miR-187 expression alternation were in accordance with their approved regulatory roles, therefore these miRNAs could serve as new biomarkers with potential usefulness in lung cancer diagnosis and treatments. In addition, miR-187 expression in tumor cells could perturb cell cycle which supported its possible role as tumor suppressor.

Keywords: Biomarkers; Development related miRNAs; Lung cancer; Tumor marker; miR-134; miR-187.