miRNA expression profiling of lung adenocarcinomas: correlation with mutational status

Abstract

MicroRNA (miRNA) expression is deregulated in lung cancer, and some miRNAs are associated with poor prognosis and survival. In this study, we investigated the miRNA expression in lung adenocarcinomas with different oncogenic mutations, including EGFR-positive, KRAS-positive and EGFR/KRAS-negative tumors. The expression of 319 miRNAs was evaluated by Exiqon/Luminex microarray, and expression of individual miRNAs was validated by individual RT-PCR assays (Applied Biosystems). Overall, miRNA expression was similar among three mutationally different groups with most upregulated miRNAs being miR-20a, miR-328, miR-34c and miR-18b and most downregulated miRNAs being miR-32, miR-137 and miR-342. Four miRNAs (miR-155, miR-25, miR-495 and miR-7g) were expressed differently among these tumors. miR-155 was upregulated only in EGFR/KRAS-negative group, miR-25 was upregulated only in EGFR-positive group and miR-495 was upregulated only in KRAS-positive adenocarcinomas. In opposite, let-7g was downregulated in all three groups, with more significant downregulation in EGFR/KRASnegative adenocarcinomas. Principal component analysis (PCA) revealed significant correlation between miRNA expression patterns and somatic mutations. In this study, we demonstrated that despite the similarity in miRNA expression among lung adenocarcinomas with different somatic mutations, some miRNAs showed unique expression patterns, which were in strong correlation with the mutation type, suggesting different carcinogenic pathway for these tumors. These miRNAs can be further explored for their diagnostic and prognostic use.

Let-7g and miR-21 expression in non-small cell lung cancer: Correlation with clinicopathological and molecular features

“…In our study, the frequency of K-Ras mutation (20.5%) was in agreement with previously reported data (34,35), whereas EGFR mutation incidence was slightly higher (29.5%) than that reported in the literature for lung cancer (15-20%) (6,(36)(37)(38), because many of the recruited patients belonged to a larger study designed to evaluate the EGFR TKI response. According to previously reported data (20,21,30,39), Let-7g expression was not correlated with EGFR or K-Ras mutational status. However, several studies have demonstrated that Let-7g acts as a K-Ras negative regulator by binding to multiple sites of their 3'UTRs (40) and that lung cancer tissues with reduced Let-7g levels have significantly higher K-Ras levels compared to their corresponding normal tissues (18,20).…”

miR-137 inhibits the proliferation of human non-small cell lung cancer cells by targeting SRC3

“…It has been revealed that miRNAs can downregulate gene expression by binding to the 3' untranslated regions (3'UTRs) of mRNA (6), thus affecting the proliferation, and metastasis of numerous types of cancer, such as gastric (7), breast (8) and lung cancer (9,10). The expression of miR-137 has been identified to be significantly downregulated in lung cancer compared with healthy lung tissue (11). Similar results have been identified in glioblastoma (12) and colorectal cancer (13).…”

Prognostic Implications for High Expression of MiR-25 in Lung Adenocarcinomas of Female Non-smokers

“…This result is in agreement with the finding of Dacic's study which investigated the miRNA expression in lung adenocarcinomas with different oncogenic mutations, including EGFR-positive, KRAS-positive and EGFR/ KRAS-negative tumors. Their results showed miR-25 was up-regulated in EGFR-positive group (Dacic et al, 2010). It is known that activating EGFR mutations are common in patients with ADC histological type who are female never smokers and Asian ethnicity (Lynch et al, 2004;Pao et al, 2004).…”