MicroRNA-9 enhanced radiosensitivity and its mechanism of DNA methylation in non-small cell lung cancer

Wei, Wei; Dong, Zuo-Ren; Gao, Hui; Zhang, Yuyu; Shao, Lihong; Jin, Lei; Lv, Yahui; Zhang, Gang; Shen, Yan; Jin, Shunzi

doi:10.1016/j.gene.2019.05.050

Cited by 32 publications

(20 citation statements)

References 44 publications

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“…Additionally, miR-9 overexpression increased the radio-sensitivity of A549 cells by inhibiting cell activity and migration, and by increasing apoptosis. Accordingly, the promoter methylation status of the microRNA-9 gene increased in response to ionizing radiation [92].…”

Section: Epigenetic Factors In the Development Of Radon-induced Lung mentioning

confidence: 99%

Radon Biomonitoring and microRNA in Lung Cancer

Bersimbaev

Pulliero

Bulgakova

et al. 2020

IJMS

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Radon is the number one cause of lung cancer in non-smokers. microRNA expression in human bronchial epithelium cells is altered by radon, with particular reference to upregulation of miR-16, miR-15, miR-23, miR-19, miR-125, and downregulation of let-7, miR-194, miR-373, miR-124, miR-146, miR-369, and miR-652. These alterations alter cell cycle, oxidative stress, inflammation, oncogene suppression, and malignant transformation. Also DNA methylation is altered as a consequence of miR-29 modification induced by radon. Indeed miR-29 targets DNA methyltransferases causing inhibition of CpG sites methylation. Massive microRNA dysregulation occurs in the lung due to radon expose and is functionally related with the resulting lung damage. However, in humans this massive lung microRNA alterations only barely reflect onto blood microRNAs. Indeed, blood miR-19 was not found altered in radon-exposed subjects. Thus, microRNAs are massively dysregulated in experimental models of radon lung carcinogenesis. In humans these events are initially adaptive being aimed at inhibiting neoplastic transformation. Only in case of long-term exposure to radon, microRNA alterations lead towards cancer development. Accordingly, it is difficult in human to establish a microRNA signature reflecting radon exposure. Additional studies are required to understand the role of microRNAs in pathogenesis of radon-induced lung cancer.

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Section: Epigenetic Factors In the Development Of Radon-induced Lung mentioning

confidence: 99%

Radon Biomonitoring and microRNA in Lung Cancer

Bersimbaev

Pulliero

Bulgakova

et al. 2020

IJMS

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“…Thus, it remains critical to investigate the molecular mechanism and prognostic markers of radioresistance, in order to increase effectiveness of radiotherapy. Recent studies have demonstrated an association between the radiosensitivity of cancer cells and methylation levels (13)(14)(15). Epigenetic modifications, particularly promoter hypermethylation, which results in silencing of the expression of tumor suppressor genes, contribute to the regulation of cellular events associated with cancer development and progression, such as apoptosis (16), cell cycle (17), proliferation (18) and DNA repair (19); and the mechanisms above have been identified to have an effect on radiosensitivity (20,21).…”

Section: Introductionmentioning

confidence: 99%

Aberrant methylation of GADD45A is associated with decreased radiosensitivity in cervical cancer through the PI3K/AKT signaling pathway

Meng

Lang

et al. 2020

Oncol Lett

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Epigenetic inactivation of GADD45A is a common occurrence in different types of cancer. However, little is known regarding its association with radiosensitivity in cervical cancer (CC). Thus, the present study aimed to investigate the association between aberrant GADD45A methylation and radiosensitivity in CC. SiHa, HeLa and CaSki CC cells were treated with 5-azacytidine (5-azaC), with or without irradiation. The expression levels of GADD45A and AKT related molecules were detected via reverse transcription-quantitative PCR and western blot analyses. The methylation status of GADD45A was assessed via methylation-specific PCR and cell proliferation assays, while clonogenic assays and flow cytometric analysis were performed to assess the function of the genes (GADD45A and AKT) in the CC cell lines. The results demonstrated that methylation of GADD45A was significantly higher in the radioresistant tissues (63.16%) compared with the radiosensitive samples (33.33%). In addition, the surviving fraction of SiHa cells following irradiation with 2 Gy was demonstrated to be highest amongst the three CC cells (CaSki, 57±9.5%; HeLa, 70±4% and SiHa, 75±10%). The survival rate of SiHa cells following treatment with 5-azaC and ionizing radiation (IR) significantly decreased as the radiation dose increased, compared with treatment with IR alone. Following overexpression of GADD45A or treatment with 5-azaC, the radiosensitivity of SiHa cells significantly increased compared with both the control vector and PBS treated groups. In addition, the AKT inhibitor, MK-2206, increased the radiosensitivity of SiHa cells. Notably, aberrant methylation of GADD45A was associated with decreased radiosensitivity in CC, and the PI3K/AKT signaling pathway was essential for radioresistance, which was mediated through downregulation of GADD45A.

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“…Conversely, miR-9 has been described as a tumor suppressor by targeting NF-kB (nuclear factor kappa light polypeptide) in gastric carcinoma [14], preventing cell proliferation in epithelial ovarian cancer [15], and inducing cell apoptosis and decreasing migration in lung adenocarcinoma cell line overexpressing miR-9 [16]. miR-9 also inhibits cell metastasis and EMT through targeting the forkhead box P2 (FOXP2) in colorectal carcinoma, and its downregulation is correlated with a poor prognosis [17].…”

Section: Introductionmentioning

confidence: 99%

“…The growth inhibitory effect of Erlotinib was reduced with ectopic overexpression of miR-9 in adenocarcinoma cell lines [23]. On the contrary, miR-9 overexpression in the A549 (NSCLC) cell line enhanced cisplatin sensitivity by targeting the eukaryotic translation initiation factor 5A2 [28] and improved the efficiency of ionizing radiation treatment [16]. This disparity may be the result of variations in miR-9 genes' methylation, an epigenetic mechanism, leading to transcriptional silencing.…”

Section: Introductionmentioning

confidence: 99%

“…This disparity may be the result of variations in miR-9 genes' methylation, an epigenetic mechanism, leading to transcriptional silencing. Erlotinib activates microRNA-9-1 methylation, inhibiting its transcription [29], and radiation enhances the DNA methylation of the microRNA-9-3 promoter [16]. Moreover, no solid concept has been established regarding the prognostic value of miR-9 genes methylation in NSCLC [23,[29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

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miR-9 Does Not Regulate Lamin A Expression in Metastatic Cells from Lung Adenocarcinoma

Guinde

Benoit

Frankel

et al. 2020

IJMS

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In lung adenocarcinoma, low lamin A expression in pleural metastatic cells has been proposed as a pejorative factor. miR-9 physiologically inhibits the expression of lamin A in neural cells and seems to be a central actor in the carcinogenesis and the metastatic process in lung cancer. Thus, it could be a good candidate to explain the reduction of lamin A expression in lung adenocarcinoma cells. miR-9 expression was analyzed in 16 pleural effusions containing metastatic cells from lung adenocarcinoma and was significantly reduced in patients from the ‘Low lamin A expression’ group compared to patients from the ‘High lamin A expression’ group. Then, carcinoma cells selection by fluorescence-activated cell sorting (FACS) was performed according to epithelial membrane antigen (EMA) expression, reflecting lamin A expression. miR-9 was underexpressed in lamin A− carcinoma cells compared to lamin A+ carcinoma cells in patients from the ‘Low lamin A expression’ group, whereas there was no difference of miR-9 expression between lamin A+ and lamin A− carcinoma cells in patients from the ‘High lamin A expression’ group. These results suggest that miR-9 does not regulate lamin A expression in metastatic cells from lung adenocarcinoma. On the contrary, miR-9 expression was shown to be reduced in lamin A-negative carcinoma cells.

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MicroRNA-9 enhanced radiosensitivity and its mechanism of DNA methylation in non-small cell lung cancer

Cited by 32 publications

References 44 publications

Radon Biomonitoring and microRNA in Lung Cancer

Radon Biomonitoring and microRNA in Lung Cancer

Aberrant methylation of GADD45A is associated with decreased radiosensitivity in cervical cancer through the PI3K/AKT signaling pathway

miR-9 Does Not Regulate Lamin A Expression in Metastatic Cells from Lung Adenocarcinoma

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