MicroRNA-124 regulates the radiosensitivity of non-small cell lung cancer cells by targeting TXNRD1

Abstract

Radiation treatment remains one of the major modalities in the treatment of lung cancer. Although the majority of patients initially respond to treatment with radiation, resistance inevitably develops and leads to treatment failure. Therefore, the identification of the underlying molecular mechanisms of radiation resistance may facilitate the development of novel approaches for overcoming resistance, and enhance the efficacy of treatment with radiation in lung and other types of cancer. In the present study we established three radiation-resistant sub-cell lines derived from the radiation-sensitive lung cancer cell line HCC827. Using a polymerase chain reaction microRNA (miRNA) array, multiple miRNAs were identified to be markedly downregulated in radiation-resistant cells, including miRNA (miR)-124, miR-191 and miR-205. It was observed that overexpression of miR-124 sensitized the resistant cells to treatment with radiation and that thioredoxin reductase 1 (TXNRD1) is a novel target of miR-124. Furthermore, it was demonstrated that knockdown of TXNRD1 using small interfering RNA increased the basal level of reactive oxygen species and sensitized the cells to radiation treatment. The results of the present study demonstrated that multiple miRNAs are downregulated in radiation-resistant lung cancer cells and that downregulation of miR-124 mediates radiation resistance through the targeting of TXNRD1 mRNA expression. The present study revealed a novel molecular mechanism of miRNA-mediated radiation resistance and identified miR-124-regulated TXNRD1 as a novel therapeutic target for overcoming radiation resistance in the treatment of lung cancer.

The lncRNA MALAT1 contributes to non‐small cell lung cancer development via modulating miR‐124/STAT3 axis

“…miR‐146b‐5p can inhibit NSCLC by targeting MMP16 and TRAF6 (Li, Zhang, et al, ). miR‐124 can regulate the radiosensitivity of NSCLC by targeting TXNRD1 (Hao et al, ). miR‐124 can suppress NSCLC progression by inhibiting CD164 signaling (Lin et al, ).…”

MicroRNA-148b enhances the radiosensitivity of B-cell lymphoma cells by targeting Bcl-w to promote apoptosis

“…MiRNAs are critical to cell growth, development, proliferation, differentiation, and death [17]. Growing evidence has demonstrated that miRNAs are involved in the regulation of tumor radiosensitivity [18][19][20][21][22][23][24][25][26][27]. It has previously been reported that miR-148b acts as a tumor suppressor in the context of lung cancer [28], cervical cancer [29], and gastric cancer [30].…”

Circ0120816 acts as an oncogene of esophageal squamous cell carcinoma by inhibiting miR-1305 and releasing TXNRD1

“…TXNRD1 was widely reported to participate in the positive regulation of hepatocellular carcinoma [ 58 – 60 ]. In addition, TXNRD1 was observed to contribute to the development of lung cancer [ 61 ] and breast cancer [ 62 , 63 ]. However, researchers are yet to provide detailed explanations regarding the relationship between TXNRD1 and ESCC.…”