Inhibition of miR-191 contributes to radiation-resistance of two lung cancer cell lines by altering autophagy activity

Liu, Zhenkuan; Shao-xiang, Huang

doi:10.1186/s12935-015-0165-5

Cited by 20 publications

(11 citation statements)

References 38 publications

(37 reference statements)

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“… 42 Moreover, it impairs tumorigenesis and metastasis in aggressive breast cancer 43 and inhibits radiation-resistance in lung cancer. 44 In our study, multivariate analysis revealed decreased expression of miR-191-5p was associated with poor survival and tumor recurrence in patients with COAD and acted as an independent prognostic factor for OS in COAD patients. Our findings regarding the prognosis and diagnostic potentials of miR-191-5p in COAD were supported by these studies in renal cell carcinoma, breast cancer, and lung cancer, 41 – 44 but opposed by other studies in AML, 37 hepatic cell carcinoma, 38 and intrahepatic cholangiocarcinoma.…”

Section: Discussionsupporting

confidence: 50%

Upregulation of PD-L1 predicts poor prognosis and is associated with miR-191-5p dysregulation in colon adenocarcinoma

Chen

Zhang

Hou

et al. 2018

Int J Immunopathol Pharmacol

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Targeting of the programmed cell-death 1 ligand 1 (PD-L1) signal pathway is a promising treatment strategy in several cancers. The purpose of this study was to evaluate the clinical significance of PD-L1 in patients with colon adenocarcinoma (COAD). A total of 240 patients who were diagnosed with COAD from The Cancer Genome Atlas (TCGA) RNA-sequencing data and another cohort for pair-matched COAD samples (n = 40) in tissue microarray (TMA) were enrolled in this study. The correlation of PD-L1 or miR-191-5p expression with clinicopathological features and prognosis in patients with COAD was further analyzed using TCGA data and TMA. The Cox proportional hazard regression model was used to evaluate the association of PD-L1 or miR-191-5p expression with overall survival (OS) and tumor recurrence in patients with COAD. The microRNAs (miRNAs) that target PD-L1 gene were identified by bioinformatics and Spearman correlation analysis. We found that PD-L1 expression was increased in COAD tissues and was correlated with poor survival and tumor recurrence in patients with COAD. The increased expression of PD-L1 was attributed to the dysregulation of miR-191-5p expression rather than its genetic or epigenetic alterations. Moreover, the expression of miR-191-5p presented the negative correlation with PD-L1 expression and acted as an independent prognostic factor of OS in patients with COAD. Therefore, PD-L1 may predict poor prognosis and is negatively associated with miR-191-5p expression in patients with COAD.

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Section: Discussionsupporting

confidence: 50%

Upregulation of PD-L1 predicts poor prognosis and is associated with miR-191-5p dysregulation in colon adenocarcinoma

Chen

Zhang

Hou

et al. 2018

Int J Immunopathol Pharmacol

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“…We selected miR-140 as one of the most promising candidates for further analysis because: (1) we performed in silico analysis (https://www.genomatix.de/) and identified a putative NRF2 binding site in the miR-140 promoter region (−7844/−7835, the transcription start site set as default +1) (Fig. 3B, top panel); (2) miR-140 is significantly upregulated in lung cancer cells in response to irradiation [25]; and (3) miR-140 inhibits proliferation and stem cell self-renewal [26]. q-PCR analysis showed an increased expression level of miR-140 in irradiated HLFs.…”

Section: Resultsmentioning

confidence: 99%

NRF2/miR-140 signaling confers radioprotection to human lung fibroblasts

et al. 2015

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Breast and lung cancer patients who are treated with radiotherapy often have severe side effects, including radiation-induced lung damage and secondary cancers. Activation of the NRF2 pathway is a well-known mechanism that protects cells against radiation induced oxidative stress, but its role in radiation-induced lung damage is not well understood. Using human lung fibroblasts (HLFs) we found that ionizing radiation (IR) leads to BRCA1-dependent activation of NRF2 through the inhibition of KEAP1 function, promoting the nuclear accumulation of NRF2, and activating critical radioprotective mechanisms. We discovered that NRF2 directly binds to the miR-140 promoter and increases its expression in response to IR treatment. Gain and loss of function studies further showed the ability of miR-140 to regulate lung fibroblast self-renewal upon irradiation, a potential mechanism to contribute to the regulation of DNA repair. We verified our in vitro findings using primary lung fibroblast cultures from wild type and Nrf2 (KO) mice. Using these models we showed that IR induces overexpression of Brca1, Nrf2 and miR-140 in lung tissue after irradiation. These data reveal a novel radioprotective mechanism in which IR promotes NRF2 nuclear translocation and subsequent activation of miR-140 transcription in HLFs.

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“…miR-124 was identified to be significantly downregulated in radiation-resistant sub-cell lines. Other downregulated miRNAs included miR-191 and miR-205, which have been reported previously to be involved in radiation resistance in lung and breast cancer, respectively ( 14 , 15 ). It was demonstrated that overexpression of miR-124 was able to sensitize radiation-resistant cells to radiation by decreasing the cell survival fraction and viability, and identified that TXNRD1 is an important target of miR-124.…”

Section: Discussionmentioning

confidence: 95%

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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Inhibition of miR-191 contributes to radiation-resistance of two lung cancer cell lines by altering autophagy activity

Cited by 20 publications

References 38 publications

Upregulation of PD-L1 predicts poor prognosis and is associated with miR-191-5p dysregulation in colon adenocarcinoma

Upregulation of PD-L1 predicts poor prognosis and is associated with miR-191-5p dysregulation in colon adenocarcinoma

NRF2/miR-140 signaling confers radioprotection to human lung fibroblasts

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

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