Abberent expression of oncogenic and tumor-suppressive microRNAs and their target genes in human adenocarcinoma alveolar basal epithelial cells
Elham Tafsiri1, Mojtaba Darbouy2, Mohammad Behgam Shadmehr3, William C Cho4, Morteza Karimipoor5
1 Department of Molecular Genetics, Science and Research Branch, Islamic Azad University, Fars; Department of Molecular Medicine, Biotechnology Research Center, Pasture Institute of Iran, Tehran, Iran
2 Department of Molecular Genetics, Science and Research Branch, Islamic Azad University, Fars, Tehran, Iran
3 Department of Medical Science, Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong
5 Department of Molecular Medicine, Biotechnology Research Center, Pasture Institute of Iran, Tehran, Iran
Department of Molecular Medicine, Biotechnology Research Center, Pasture Institute of Iran, 1316943551 Pasteur Institute of Iran, Tehran
Source of Support: None, Conflict of Interest: None
Context: Lung cancer is one of the most serious types of cancer that often diagnosed at advanced stage. MicroRNAs (miRNAs) are small non-coding molecules which silence gene expression of target gene (s) at posttranscriptional level. They are key regulators of cell cycle, apoptosis, anti-cancer drug responsiveness and metastasis.
Aims: Identification of the differential expression level of miR-15a/16, miR-21, miR-34a, miR-126, miR-128 and miR-210 in A549 cell line versus normal tissues and their correlation with selected corresponding target genes.
Materials and Methods: A549 cell line was cultured in F-12K medium and miRNA was extracted from normal tissues (2-3 cm adjacent to tumor tissue) and A549 cell line. cDNA was synthesized with specific stem-loop primers for each miRNA, while OligodT primer was used for target genes cDNA synthesis. Real-time quantitative polymerase chain reaction. (RT-qPCR) was used to analyze the expression pattern of miRNAs and target genes in A549 and normal non-small cell lung carcinoma. (NSCLC) tissues.
Results: miR-15a/16, miR-34a, miR-126 and miR-128 were down-regulated significantly. (>2-fold change), while miR-21 and miR.210 were up-regulated in A549. Bcl-2 as miR-34a target gene was down-regulated while Hif-1α and Akt-3 were up-regulated that might be miR-210 and miR-34a target genes, respectively.
Conclusion: The significant differential expression level of these miRNAs made them as candidate biomarkers in NSCLC tumor tissues of patients. Perhaps Bcl-2 down-regulation and Akt-3 up-regulation can be linked with survival signals in A549 cell line. We can conclude that Bcl-2 and Akt-3 might be therapeutic targets to inhibit cell proliferation in NSCLC.