MiRNA-218-5p Increases Cell Sensitivity by Inhibiting PRKDC Activity in Radiation-resistant Lung Carcinoma Cells

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2021 Mar 24

PMID 33759399

Citations 9

Authors

Xiaoke Chen

Yuanyuan Xu

Long Jiang

Qiang Tan

Affiliations

Soon will be listed here.

Abstract

Background: Non-small cell lung carcinoma (NSCLC) is a malignancy with the highest mortality rate. Currently, surgery combined with radiotherapy is the first choice in the clinical treatment of lung carcinoma (LC); however, long-term radiotherapy leads to radiation resistance in patients, resulting in treatment failure.

Methods: In this study, a new microRNA-218-5p (miRNA-218-5p) was identified, and its function in LC was investigated.

Results: Reverse transcription quantitative polymerase chain reaction (RT-qPCR) results revealed that miRNA-218-5p was downregulated in LC. Overexpression or inhibition of miRNA-218-5p in LC and targeted binding of protein kinase, DNA-activated, catalytic polypeptide (PRKDC) to miRNA-218-5p were confirmed by comprehensive bioinformatic analysis. Exosomes from A549 and H1299 cells were cocultured with miRNA-218-5p and then cotransfected into radiation-resistant A549R and H1299R cells; the proliferation of radiation-resistant LC cells was found to be effectively inhibited and apoptosis was induced. Overexpression of miRNA-218-5p and X-irradiation could enhance the radiosensitivity of LC cells. Exogenous miRNA-218-5p derived from A549 and H1299 cells could be transfected into radiation-resistant LC cells and could inhibit PRKDC expression, thus accelerating DNA damage, apoptosis, and radiation sensitization of LC cells.

Conclusions: miRNA-218-5p could induce apoptosis and enhance the radiosensitivity of LC cells through regulatory activities, thus suggesting its application as a potential target for LC treatment.

Citing Articles

Myeloid cell differentiation-related gene signature for predicting clinical outcome, immune microenvironment, and treatment response in lung adenocarcinoma.

Wu D, Liu Y, Liu J, Ma L, Tong X Sci Rep. 2024; 14(1):17460.

PMID: 39075165 PMC: 11286868. DOI: 10.1038/s41598-024-68111-5.

miRNAs in radiotherapy resistance of cancer; a comprehensive review.

Al-Hawary S, Jasim S, Altalbawy F, Kumar A, Kaur H, Pramanik A Cell Biochem Biophys. 2024; 82(3):1665-1679.

PMID: 38805114 DOI: 10.1007/s12013-024-01329-2.

Exosomal microRNA Therapy for Non-Small-Cell Lung Cancer.

Chen J, Wu F, Hou E, Zeng J, Li F, Gao H Technol Cancer Res Treat. 2023; 22:15330338231210731.

PMID: 37936417 PMC: 10631355. DOI: 10.1177/15330338231210731.

Role of the antineoplastic drug bleomycin based on toxicogenomic-DNA damage inducing (TGx-DDI) genomic biomarkers data: A meta-analysis.

Pushparaj P, Rasool M, Naseer M, Gauthaman K Pak J Med Sci. 2023; 39(2):423-429.

PMID: 36950431 PMC: 10025729. DOI: 10.12669/pjms.39.2.7321.

MicroRNAs and Drug Resistance in Non-Small Cell Lung Cancer: Where Are We Now and Where Are We Going.

Cuttano R, Afanga M, Bianchi F Cancers (Basel). 2022; 14(23).

PMID: 36497213 PMC: 9740066. DOI: 10.3390/cancers14235731.

References

Lemjabbar-Alaoui H, Hassan O, Yang Y, Buchanan P . Lung cancer: Biology and treatment options. Biochim Biophys Acta. 2015; 1856(2):189-210. PMC: 4663145. DOI: 10.1016/j.bbcan.2015.08.002. View

Yang Q, Li J, Hu Y, Tang X, Yu L, Dong L . MiR-218-5p Suppresses the Killing Effect of Natural Killer Cell to Lung Adenocarcinoma by Targeting SHMT1. Yonsei Med J. 2019; 60(6):500-508. PMC: 6536398. DOI: 10.3349/ymj.2019.60.6.500. View

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

Chen X, Xu Y, Jiang L, Tan Q . miRNA-218-5p increases cell sensitivity by inhibiting PRKDC activity in radiation-resistant lung carcinoma cells. Thorac Cancer. 2021; 12(10):1549-1557. PMC: 8107034. DOI: 10.1111/1759-7714.13939. View

Steven A, Fisher S, Robinson B . Immunotherapy for lung cancer. Respirology. 2016; 21(5):821-33. DOI: 10.1111/resp.12789. View

Meng F, Zhang L . miR-183-5p functions as a tumor suppressor in lung cancer through PIK3CA inhibition. Exp Cell Res. 2018; 374(2):315-322. DOI: 10.1016/j.yexcr.2018.12.003. View

Chua G, Lee Min Chua K . Which patients benefit most from stereotactic body radiotherapy or surgery in medically operable non-small cell lung cancer? An in-depth look at patient characteristics on both sides of the debate. Thorac Cancer. 2019; 10(10):1857-1867. PMC: 6775005. DOI: 10.1111/1759-7714.13160. View

Zhu Y, Wang C, Becker S, Hurst K, Nogueira L, Findlay V . miR-145 Antagonizes SNAI1-Mediated Stemness and Radiation Resistance in Colorectal Cancer. Mol Ther. 2018; 26(3):744-754. PMC: 5910672. DOI: 10.1016/j.ymthe.2017.12.023. View

Yin H, Ma J, Chen L, Piao S, Zhang Y, Zhang S . MiR-99a Enhances the Radiation Sensitivity of Non-Small Cell Lung Cancer by Targeting mTOR. Cell Physiol Biochem. 2018; 46(2):471-481. DOI: 10.1159/000488615. View

10.

Yang Y, Ding L, Hu Q, Xia J, Sun J, Wang X . MicroRNA-218 functions as a tumor suppressor in lung cancer by targeting IL-6/STAT3 and negatively correlates with poor prognosis. Mol Cancer. 2017; 16(1):141. PMC: 5567631. DOI: 10.1186/s12943-017-0710-z. View

11.

Villalobos P, Wistuba I . Lung Cancer Biomarkers. Hematol Oncol Clin North Am. 2016; 31(1):13-29. PMC: 5137804. DOI: 10.1016/j.hoc.2016.08.006. View

12.

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

13.

Iwamoto N, Fukui S, Takatani A, Shimizu T, Umeda M, Nishino A . Osteogenic differentiation of fibroblast-like synovial cells in rheumatoid arthritis is induced by microRNA-218 through a ROBO/Slit pathway. Arthritis Res Ther. 2018; 20(1):189. PMC: 6116572. DOI: 10.1186/s13075-018-1703-z. View

14.

Koritzinsky E, Street J, Star R, Yuen P . Quantification of Exosomes. J Cell Physiol. 2016; 232(7):1587-1590. PMC: 5039048. DOI: 10.1002/jcp.25387. View

15.

Storch K, Dickreuter E, Artati A, Adamski J, Cordes N . BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage. PLoS One. 2016; 11(12):e0167931. PMC: 5154536. DOI: 10.1371/journal.pone.0167931. View

16.

Romaszko A, Doboszynska A . Multiple primary lung cancer: A literature review. Adv Clin Exp Med. 2018; 27(5):725-730. DOI: 10.17219/acem/68631. View

17.

Watanabe S, Nakagawa K, Suzuki K, Takamochi K, Ito H, Okami J . Neoadjuvant and adjuvant therapy for Stage III non-small cell lung cancer. Jpn J Clin Oncol. 2017; 47(12):1112-1118. DOI: 10.1093/jjco/hyx147. View

18.

Wu L, Hu B, Zhao B, Liu Y, Yang Y, Zhang L . Circulating microRNA-422a is associated with lymphatic metastasis in lung cancer. Oncotarget. 2017; 8(26):42173-42188. PMC: 5522058. DOI: 10.18632/oncotarget.15025. View

19.

Gilligan K, Dwyer R . Engineering Exosomes for Cancer Therapy. Int J Mol Sci. 2017; 18(6). PMC: 5485946. DOI: 10.3390/ijms18061122. View

20.

Jin X, Liu X, Zhang Z, Guan Y . lncRNA CCAT1 Acts as a MicroRNA-218 Sponge to Increase Gefitinib Resistance in NSCLC by Targeting HOXA1. Mol Ther Nucleic Acids. 2020; 19:1266-1275. PMC: 7029377. DOI: 10.1016/j.omtn.2020.01.006. View