Silencing miR-21 Sensitizes Non-Small Cell Lung Cancer A549 Cells to Ionizing Radiation through Inhibition of PI3K/Akt

Ma, Yongfu; Xia, Hui; Liu, Yang; Li, Min

doi:10.1155/2014/617868

Cited by 48 publications

(33 citation statements)

References 38 publications

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“…Thus, effective treatment that sensitizes radioresistant NSCLC to radiotherapy is urgently needed [13]. Recent research has reported that the many miRNAs affect the radiosensitivity of NSCLC cells, which may be associated with apoptosis inhibition [17, 20].…”

Section: Discussionmentioning

confidence: 99%

“…As an oncomicroRNA involved in tumor progression, microRNA-21-5p (miR-21-5p) is a potential therapeutic target in lung cancer [12]. Overexpression of miR-21-5p has been found in many human malignancies, including NSCLC [13]. For example, high expression of miR-21-5p enhances viability, invasion, viability, and migration of an NSCLC cell line (NCI-H157), and down-regulation of miR-21-5p significantly decreases the levels of certain protein in these cells [12].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of MicroRNA-21-5p Promotes the Radiation Sensitivity of Non-Small Cell Lung Cancer Through HMSH2

Zuo

Qian

et al. 2017

Cell Physiol Biochem

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Background: This study aimed to explore the effects of microRNA-21-5p (miR-21-5p) on the radiation sensitivity of non-small cell lung cancer (NSCLC) and the involvement of human MutS homolog 2 (hMSH2) One hundred fourteen NSCLC patients at stage II or III who received surgery and postoperative radiotherapy were enrolled in this study. Methods: The patients were assigned into radiation-sensitive and -insensitive groups. NSCLC A549 cells were transfected to generate control, Negative control (NC), miR-21-5p inhibitor, miR-21-5p mimic, small interfering hMSH2 (sihMSH2), miR-21-5p inhibitor + sihMSH2 and hMSH2 overexpression groups. Immunohistochemistry was performed to detect the hMSH2 expression in transfected and irradiated cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to evaluate A549 miR-21-5p and hMSH2 expression in transfected and irradiated cells. A colony formation assay was adopted for cell survival analysis. The relationship between miR-21-5p and hMSH2 was verified by a luciferase reporter assay. Cell viability was measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and apoptosis was assessed by flow cytometry. NSCLC nude mouse models were established, and tumor volumes and tumor weights were recorded. Results: The radiation-sensitive group of patients exhibited lower miR-21-5p but higher hMSH2 expression than the insensitive group. For irradiated A549 cells, lower cell survival, higher apoptosis, increased miR-21-5p expression and decreased hMSH2 expression were observed at 6 and 8 Gy than at 0, 2 and 4 Gy; compared to 6 Gy, cell survival and hMSH2 expression were decreased and apoptosis and miR-21-5p expression were increased at 8 Gy. Additionally, miR-21-5p was found to target hMSH2. Compared with the control group, the cell survival rate was lower and the apoptosis rate higher in the miR-21-5p inhibitor group, whereas the opposite was observed for the miR-21-5p mimic and sihMSH2 groups. For the mouse model, decreased tumor volume and tumor weight and higher hMSH2 expression were found in the miR-21-5p inhibitor, radiation, hMSH2 overexpression, miR-21-5p inhibitor + radiation and hMSH2 overexpression + radiation groups compared with the control group. In addition, tumor volume and tumor weight were decreased and hMSH2 expression increased in the miR-21-5p inhibitor + radiation and hMSH2 overexpression + radiation groups compared with the radiation alone group. Conclusion: These findings indicate that inhibition of miR-21 can promote the radiation sensitivity of NSCLC by targeting hMSH2.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of MicroRNA-21-5p Promotes the Radiation Sensitivity of Non-Small Cell Lung Cancer Through HMSH2

Zuo

Qian

et al. 2017

Cell Physiol Biochem

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“…Thus, the use of miR-21 inhibitors is a strategy that may increase the sensitivity of cancer cells to radiation Ma et al 2014), but its potential impact on surrounding non cancer cells is still unexplored.…”

Section: Discussionmentioning

confidence: 99%

Differential response of normal and transformed mammary epithelial cells to combined treatment of anti-miR-21 and radiation

Radulović

Heider

Richter

et al. 2017

International Journal of Radiation Biology

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Purpose: MicroRNA miR-21 has emerged as a therapeutic target in the treatment of breast cancer. This study was designed to compare the responses of breast cancer cells and non-transformed breast epithelial cells to a combined regimen of miR-21 inhibition and radiation. Materials and methods: The MDA-MB-361 (breast cancer) and MCF-10A (non-transformed mammary epithelial) cell lines were used for the comparison in this in vitro study. The stable knockdown of miR-21 was performed by using lentiviral approach. The response of the cells was monitored 4, 24 and 48 h after the irradiation with 0.25 and 2.5 Gy, using sham-irradiated cells as controls. The response of the cells was established by performing various functional assays -cell viability and cell attachment, clonogenic survival, cell cycle analysis and 3D microtissue formation. Results: The knockdown of miR-21 induced significant increase in apoptosis and growth delay in MDA-MB-361 cancer cells compared to non-transformed MCF-10A cells. After combined radiation and anti-miR-21 treatment, MDA-MB-361 cells show reduced cell growth and viability what is presented in their inability to form colonies. MCF-10A cells were not as sensitive to the combined treatment and that has also been confirmed with colony forming assay. Conclusions: Cellular response to a combined treatment of anti-miR-21 and radiation is different between cancer and non-cancer cells which highly support the idea of linking miR-21 inhibitor and radiation treatment in the future therapeutic approaches for breast cancer. ARTICLE HISTORY

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“…Long et al demonstrated that ZM447439, a small molecular inhibitor of Aurora-B, induces cell apoptosis and inhibits cell proliferation by decreasing AKT phosphorylation at Ser473 in Hep2 cancer cells (21). Accumulated data has revealed that the PI3K/AKT signaling pathway plays a key role in NSCLC malignant behavior (22)(23)(24). Therefore, it was hypothesized that silencing Aurora-B may decrease the activity of the PI3K/AKT signaling pathway in NSCLC cells.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Aurora-B inhibits the growth of non-small cell lung cancer A549 cells

Zhou

Zhao

et al. 2015

Oncology Letters

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Silencing miR-21 Sensitizes Non-Small Cell Lung Cancer A549 Cells to Ionizing Radiation through Inhibition of PI3K/Akt

Cited by 48 publications

References 38 publications

Inhibition of MicroRNA-21-5p Promotes the Radiation Sensitivity of Non-Small Cell Lung Cancer Through HMSH2

Inhibition of MicroRNA-21-5p Promotes the Radiation Sensitivity of Non-Small Cell Lung Cancer Through HMSH2

Differential response of normal and transformed mammary epithelial cells to combined treatment of anti-miR-21 and radiation

Knockdown of Aurora-B inhibits the growth of non-small cell lung cancer A549 cells

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