miR-219a-5p enhances the radiosensitivity of non-small cell lung cancer cells through targeting CD164.
Autor: | Wei T; Department of Radiation, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang 455000, China., Cheng S; Department of Histology and Embryology, Xinxiang Medical University, Xinxiang 453000, China., Fu XN; Department of Radiation, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang 455000, China., Feng LJ; Department of Radiation, Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang 455000, China. |
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Jazyk: | angličtina |
Zdroj: | Bioscience reports [Biosci Rep] 2020 Jul 31; Vol. 40 (7). |
DOI: | 10.1042/BSR20192795 |
Abstrakt: | Lung cancer is one of the leading causes of cancer-associated mortality. Non-small cell lung carcinoma (NSCLC) accounts for 70-85% of the total cases of lung cancer. Radioresistance frequently develops in NSCLC in the middle and later stages of radiotherapy. We investigated the role of miR-219a-5p in radioresistance of NSCLC. miR-219a-5p expression in serum and lung tissue of lung cancer patients was lower than that in control. Compared with radiosensitive (RS) NSCLC patients, miR-219a-5p expression was decreased in serum and lung tissue in radioresistant patients. miR-219a-5p expression level was negatively associated with radioresistance in NSCLC cell lines. Up-regulation of miR-219a-5p increased radiosensitivity in radioresistant NSCLC cells in vitro and in vivo. Down-regulation of miR-219a-5p decreased radiosensitivity in radiosensitive A549 and H358 cells. miR-219a-5p could directly bind in the 3'UTR of CD164 and negatively regulated CD164 expression. CD164 expression was higher in radioresistant NSCLC tissues than RS tissues. Up-regulation of CD164 significantly inhibited miR-219a-5p-induced regulation of RS in radioresistant A549 and H358 cells. Down-regulation of CD164 significantly inhibited the effect of anti-miR-219a-5p on radiosensitive A549 and H358 cells. miR-219a-5p or down-regulation of CD164 could increase apoptosis and γ-H2A histone family member X (γ-H2AX) expression in radioresistant cells in vitro and in vivo. Up-regulation of CD164 could inhibit the effect of miR-219a-5p on apoptosis and γ-H2AX expression. Our results indicated that miR-219a-5p could inhibit CD164, promote DNA damage and apoptosis and enhance irradiation-induced cytotoxicity. The data highlight miR-219a-5p/CD164 pathway in the regulation of radiosensitivity in NSCLC and provide novel targets for potential intervention. (© 2020 The Author(s).) |
Databáze: | MEDLINE |
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