Abstract

BackgroundThe lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown.MethodsThe expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3).ResultsExpression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19–miR-130a-3p–WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines.ConclusionKnockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.

Highlights

  • The incidence of lung cancer ranks second among malignancies, just behind breast cancer

  • Results long noncoding RNAs (lncRNAs) H19 regulates the sensitivity of non-small cell lung cancer (NSCLC) cells to X‐ray and carbon ion irradiation In A549 cells and the compared radioresistant cells, the differentially expressed lncRNAs were investigated by high-throughput sequencing

  • The lncRNA H19 was upregulated in radioresistant NSCLC cells compared with A549 cells (Fig. 1A)

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Summary

Introduction

The incidence of lung cancer ranks second among malignancies, just behind breast cancer. The treatment modalities for lung cancer include surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy and so on. Despite the application of targeted therapy, immunotherapy and other treatment methods, the prognosis of lung cancer. It is crucial for us to identify key factors that lead to radioresistance and to improve the antitumor effects of radiotherapy. Combining radiation therapy with other approaches is a strategy for overcoming radioresistance and improving the tumor response to radiation in NSCLC. Suitable therapeutic targets should be identified to help improve radiosensitivity. The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. The role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown

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