Deregulated Expression of MiR-21, MiR-143 and MiR-181a in Non Small Cell Lung Cancer is Related to Clinicopathologic Characteristics or Patient Prognosis

Context: MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate the gene expressions at the posttranscriptional level, subsequently control crucial physiological processes. Recent evidence demonstrates that some miRNAs have the functions similar to oncogene or tumor suppressors, it may play important roles in tumorigenesis. MiRNA expression profiles may become useful biomarkers for cancer diagnostics, prognosis and prediction of response to treatment, and it could be a powerful tool for cancer prevention and therapeutics.

Objective: To explore the global expression profile of miRNAs in non small cell lung cancer (NSCLC) and its potential relevance to clinicopathological characteristics and prognosis.

Methods: LNA microRNA microarrays were utilized to detect miRNA expression levels in eight surgically removed lung carcinoma tissues (LCT) and their corresponding normal lung tissues (NT). After initial microarray validation by quantitative real-time reverse transcription polymerase chain reaction assays (qRT-PCR), miR-21, miR-143 and miR-181a were selected for further study in another 47 paired LCTs and matched NTs by qRT-PCR using Taqman microRNA assay.

Results: Twenty-seven microRNAs were observed to be deregulated greater than two-fold in LCT compared with NT by microarray. Consistenting with the microarray, the expression level of miR-21 by qRT-PCR was significantly higher in tumor tissues than in adjacent normal tissues (P=0.026); while miR-143 (P=0.000) and miR-181a (P=0.000) were downregulated in LCT. Interestingly, among the 47 NSCLC cases, low level expression of miR-143 was significantly correlated with smoking status (P=0.026), high miR-21 expression (hazard ratio, 5.993; 95% confidence interval, 2.518-14.264; P=0.000) and low miR-181a expression (hazard ratio, 0.328; 95% confidence interval 0.142-0.756; P=0.009) were associated with poor survival, independent of clinical covariates, including TNM staging, lymph note status.

Conclusion: Our data thus indicating the potential of miR-21, miR-143 and miR-181a as a novel diagnostic or prognostic biomarker for NSCLC. Besides, these data will guide further studies of specific microRNAs might become potential targets for therapeutic intervention.