Knock-Down of Core Proteins Regulating MicroRNA Biogenesis Has No Effect on Sensitivity of Lung Cancer Cells to Ionizing Radiation

Abstract

Recent studies underline the important role of microRNAs (miRNA) in the development of lung cancer. The main regulators of miRNA biogenesis are the ribonucleases Drosha, Dicer and Ago2. Here the role of core proteins of miRNA biogenesis machinery in the response of human non-small and small cell lung carcinoma cell lines to treatment with ionizing radiation was assessed. We found that Drosha and Dicer were expressed at higher levels in radioresistant but not in sensitive cell lines. However, down-regulation of either Dicer or Drosha had no effect on the sensitivity of cells to irradiation. Elimination of components of the RNA-induced silencing complex Ago2 and Tudor staphylococcal nuclease also did not sensitize cells to the same treatment. Thus, modulation of miRNA biogenesis machinery is not sufficient to increase the radiosensitivity of lung tumors and other strategies are required to combat lung cancer.

MicroRNAs in the ionizing radiation response and in radiotherapy

“…The obvious next question is whether they actively influence how cells deal with radiation injury. Two studies looked at miRNAs’ role on a global level by knocking down key components of the miRNA processing and silencing machinery: DROSHA, DICER, and AGO2 [44,45]. After γ-radiation, endothelial cells have increased rates of apoptosis, and knockdown of either DICER or AGO2 sensitizes them to IR [44].…”

“…After γ-radiation, endothelial cells have increased rates of apoptosis, and knockdown of either DICER or AGO2 sensitizes them to IR [44]. However, knockdown of all three proteins individually did not change the number of apoptotic cells in non-small cell lung cancer cell lines [45]. This difference could possibly be due to cell types, the degree of knockdown by siRNAs, or the doses of IR used, for instance, that differ between the two studies [44,45].…”

MicroRNAs, cancer and ionizing radiation: Where are we?

“…The distinctive sensitivity of these pathways suggests the autonomous activation of the two response pathways rather than a repaired DNA damage response. Nevertheless, Surova et al, 52 els of microRNA-103/107 are associated with metastasis and poor outcome. Functionally, microRNA-103/107 award migratory capacities in vitro and empower metastatic dissemination of otherwise non aggressive cells in vivo.…”

Potential Clinical Implications of miR-1 and miR-21 in Heart Disease and Cardioprotection

“…Surova et al [150] found up-regulated the overall expression of miRs in the cells by a higher expression of DROSHA and DICER enzymes. They revealed that these cells were more radioresistant compared to the cells with a lower expression of miRs.…”