Abstract B21: The paralogous microRNA clusters, <i>miR-17-92</i> and <i>miR-106-25</i>, are specifically overexpressed in metastatic non-small cell lung carcinomas
Authors: Katey SS Enfield, Stephen Lam, Wan L. Lam
Journal: Cancer Research (2012)

Abstract Background: Lung cancer is the cause of the most cancer-related deaths worldwide, with poor survival being largely attributed to late stage of disease at diagnosis and frequent metastasis. Understanding the mechanisms by which lung tumors metastasize could enable the development of anti-metastatic interventions or more specific therapeutics for metastatic disease. MicroRNAs (miRNAs) are major regulators of gene expression and control a wide range of cellular processes involved in metastasis, including apoptosis and cell cycle progression. Recently, increased expression of two paralogous miRNA clusters, miR-17-92 and miR-106b-25, was tied to control of these functions through antagonizing transforming growth factor-β (TGFβ) signaling. A tumor suppressive cytokine, TGFβ regulates cell cycle progression and apoptosis through activation of p21 and BIM, respectively. However, evidence suggests this regulation can be repressed by the overexpression of these microRNA clusters to promote tumor progression. To this end, we sought to determine whether or not expression of these clusters was increased in non-small cell lung cancer (NSCLC) cases positive for nodal or distant metastases compared to those with only locally invasive disease. Methods: A panel of 41 non-metastatic NSCLCs and a panel of 28 NSCLCs with nodal or distant metastases were collected along with paired adjacent non-malignant tissues. Expression analysis of miRNAs was conducted in these specimens using Illumina GaXII small RNA sequencing technologies. Matched tumor and normal miRNA normalized read count comparisons were performed for each miRNA in the miR-17-92 (miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, miR-92a-1) and miR-106b-25 (miR-106b, miR-93, miR-25) clusters (Wilcoxon Signed-Rank test p&amp;lt;0.05). Only those miRNAs that were significantly overexpressed and displayed a minimum average expression fold change of 2 were further investigated. Results: The significant overexpression of several miRNAs occurred specifically in the metastatic cohort, and included miR-20a, miR-92a-1, miR-106b and miR-93. miR-18a and miR-19a were significantly overexpressed in both tumor cohorts as compared to matched normal tissue; however, expression levels were substantially higher in the metastatic cohort and increased by 9.5 and 3 fold, respectively. miR-17 and miR-19b-1 were upregulated in both cohorts to a similar level, while expression of miR-25 was not significantly altered. Conclusion: miRNAs in the miR-17-92 and miR-106b-25 clusters, save miR-25, were significantly overexpressed in NSCLC cases positive for nodal or distant metastases. There was an overall trend of increasing involvement of miRNAs from these clusters moving from NSCLC cases without metastases to those with metastases, suggesting upregulation of these miRNAs is involved in the metastatic process. Citation Format: Katey SS Enfield, Stephen Lam, Wan L. Lam. The paralogous microRNA clusters, miR-17-92 and miR-106-25, are specifically overexpressed in metastatic non-small cell lung carcinomas [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr B21.