Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells

Li, Yong; Han, Wei; Ni, Tianming; Liang, Lu; Huang, Min; Zhang, Yu; Cao, Hui; Zhang, Hanqun; Luo, Wen; Li, Hang

doi:10.3892/or.2015.3884

Cited by 40 publications

(24 citation statements)

References 34 publications

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“…Using next-generation sequencing technology, they revealed miR-371a-5p, miR-34c-5p, and miR-1323 to be overexpressed while miR-324-3p, miR-93-3p, and miR-4501 were downregulated in radioresistant NPC cells [11]. Oncogenic feature of miR-1323 was supported also by Li et al who published that knockdown of miR-1323 restores sensitivity to radiation in radiation-resistant lung cancer cells [71], whereas miR-324-3p has been found downregulated in radioresistant NPC cells and directly targets WNT2B gene [21]. On the other hand, miR-34a, another member of the tumor suppressive miR-34 family, shows rather opposite effect on radioresistance than described in Li et al's study.…”

Section: Involvement Of Mirnas In Radioresistance Of Head and Neckmentioning

confidence: 97%

“…Moreover, our recent study suggests that miR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response such as NDFIP1 (Nedd4 Family Interacting Protein 1), RHEB (RAS homolog enriched in brain), and PPP2R5A (Protein Phosphatase 2 Regulatory Subunit B′, Alph) [70]. In lung cancer loss of miR-1323 and/or miR-18a enhances radiosensitivity whereas miR-511 has been found to suppress growth of radioresistant cell lines [71–73]. More deep study on molecular mechanisms revealed that effect induced by miR-1323 is mainly through the suppressing of PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) [71].…”

Section: Involvement Of Mirnas In Radioresistance Of Cancermentioning

confidence: 99%

“…In lung cancer loss of miR-1323 and/or miR-18a enhances radiosensitivity whereas miR-511 has been found to suppress growth of radioresistant cell lines [71–73]. More deep study on molecular mechanisms revealed that effect induced by miR-1323 is mainly through the suppressing of PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) [71]. Finally, both miR-100 and miR-124 have been found to be associated with radiosensitivity in colorectal carcinoma trough targeting PRRX1 (Paired Related Homeobox 1) [74, 75].…”

Section: Involvement Of Mirnas In Radioresistance Of Cancermentioning

confidence: 99%

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MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

et al. 2017

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Resistance to the ionizing radiation is a current problem in the treatment and clinical management of various cancers including head and neck cancer. There are several biological and molecular mechanisms described to be responsible for resistance of the tumors to radiotherapy. Among them, the main mechanisms include alterations in intracellular pathways involved in DNA damage and repair, apoptosis, proliferation, and angiogenesis. It has been found that regulation of these complex processes is often controlled by microRNAs. MicroRNAs are short endogenous RNA molecules that posttranscriptionally modulate gene expression and their deregulated expression has been observed in many tumors including head and neck cancer. Specific expression patterns of microRNAs have also been shown to predict prognosis and therapeutic response in head and neck cancer. Therefore, microRNAs present promising biomarkers and therapeutic targets that might overcome resistance to radiation and improve prognosis of head and neck cancer patients. In this review, we summarize the current knowledge of the functional role of microRNAs in radioresistance of cancer with special focus on head and neck cancer.

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Section: Involvement Of Mirnas In Radioresistance Of Head and Neckmentioning

confidence: 97%

Section: Involvement Of Mirnas In Radioresistance Of Cancermentioning

confidence: 99%

Section: Involvement Of Mirnas In Radioresistance Of Cancermentioning

confidence: 99%

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MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

et al. 2017

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“…Enhanced miR‐15a/16 promoted the radiosensitivity of lung cancer via downregulating the TLR1/NF‐ κ B pathway 60. Knockdown of miR‐1323 restored radiosensitivity by suppression of PRKDC activity in radiation‐resistant lung cancer cells 61. Our findings added another evidence that miR‐18a‐5p was involved in radiosensitivity in lung cancer cells.…”

Section: Discussionmentioning

confidence: 55%

Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α

Chen

et al. 2018

Cancer Medicine

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Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR‐18a‐5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR‐18a‐5p increased the radiosensitivity of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure. Dual luciferase report system and miR‐18a‐5p overexpression identified ataxia telangiectasia mutated (ATM) and hypoxia inducible factor 1 alpha (HIF‐1α) as the targets of miR‐18a‐5p. The mRNA and protein expressions of ATM and HIF‐1α were dramatically downregulated by miR‐18a‐5p in vitro and in vivo. Clinically, plasma miR‐18a‐5p expression was significantly higher in radiosensitive than in radioresistant group (P < .001). The cutoff value of miR‐18a‐5p >2.28 was obtained from receiver operating characteristic (ROC) curve. The objective response rate (ORR) was significantly higher in miR‐18a‐5p‐high group than in miR‐18a‐5p‐low group (P < .001). A tendency demonstrated that the median local progression‐free survival (PFS) from radiotherapy was longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .082). The median overall survival (OS) from radiotherapy was numerically longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .281). The sensitivity and specificity of plasma miR‐18a‐5p to predict radiosensitivity was 87% and 95%, respectively. Collectively, these results indicate that miR‐18a‐5p increases the radiosensitivity in lung cancer cells and CD133+ stem‐like cells via downregulating ATM and HIF‐1α expressions. Plasma miR‐18a‐5p would be an available indicator of radiosensitivity in lung cancer patients.

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“…Ionizing radiation induces DNA double strand breaks, thus miRNAs that regulate DNA damage and repair signaling pathways have been demonstrated to be involved in radiation sensitivity (27,28). miRNAs involved in cancer stem cell self-renewal, autophagy, hypoxia and survival signaling pathways also affect the radiosensitivity of cancer cells (15,29,30).…”

Section: Discussionmentioning

confidence: 99%

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

Hao

et al. 2017

Oncology Letters

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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.

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Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells

Cited by 40 publications

References 34 publications

MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

Radiosensitizing effects of miR‐18a‐5p on lung cancer stem‐like cells via downregulating both ATM and HIF‐1α

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

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