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MiR-219a-5p enhances the radiosensitivity of non-small cell lung cancer cells through targeting CD164.

ABSTRACT: 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.

SUBMITTER: Wei T

PROVIDER: S-EPMC7378263 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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miR-219a-5p enhances the radiosensitivity of non-small cell lung cancer cells through targeting CD164.

Wei Tao T Cheng Shan S Fu Xiao Na XN Feng Lian Jie LJ

Bioscience reports 20200701 7

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 expres ...[more]

PMID: 32364222

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Project description:ObjectiveTo determine the function of miR-125a-5p in laryngeal squamous cell carcinoma (LSCC), its correlation with radiation sensitivity, and the underlying regulatory mechanism.Materials and methodsWe conducted the analysis on the correlation between miR-125a-5p and head and neck squamous cell carcinoma (HNSCC) using data obtained from The Cancer Genome Atlas (TCGA). The putative gene targeted by miR-125a-5p has been identified as HK2, while the expression levels of miR-125a-5p and HK2 were measured in laryngeal cancer tissues and cells using RT-PCR. MiR-125a-5p and HK2 were introduced into the lentiviral vector and the vector was used to transfect AMC-HN-8 cells. The roles of miR-125a-5p and HK2 in LSCC and on radiosensitivity were determined by evaluating cell growth, examining colony formation, analyzing flow cytometry, and utilizing the single hit multi-target model. Western blotting was used to measure H2AX and rH2AX levels in the DNA damage response (DDR) pathway. The validation of the interaction between miR-125a-5p and HK2 was conducted through the dual-luciferase assay. To further confirm the association between miR-125a-5p and HK2, as well as its influence on radiosensitivity, rescue experiments were performed.ResultsThe expression of miR-125a-5p is downregulated in LSCC, while upregulating its expression could suppress cell growth, induce apoptosis, and enhance radiosensitivity. Additionally, HK2 exhibited high expression in LSCC and the biological function was opposite to miR-125a-5p. Western blotting analysis revealed that miR-125a-5p increased rH2AX levels and decreased H2AX levels, conversely, HK2 had the opposite effect on miR-125a-5p. These findings suggested that HK2 may serve as the target gene of miR-125a-5p. The double luciferase assay confirmed the binding of HK2 to miR-125a-5p, and rescue trials confirmed the role of miR-125a-5p in regulating the effects and radiation sensitivity of LSCC by targeting HK2 via the DDR pathway.ConclusionBy targeting HK2 and impacting the DDR pathway, miR-125a-5p has been found to inhibit cellular proliferation, enhance apoptosis, and heighten radiosensitivity in LSCC.

Dataset Information

MiR-219a-5p enhances the radiosensitivity of non-small cell lung cancer cells through targeting CD164.

Publications

miR-219a-5p enhances the radiosensitivity of non-small cell lung cancer cells through targeting CD164.

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