MicroRNA-148b enhances the radiosensitivity of non-Hodgkin's Lymphoma cells by promoting radiation-induced apoptosis

Abstract

Growing evidence has demonstrated that microRNAs (miRNAs) play an important role in regulating cellular radiosensitivity. This study aimed to explore the role of miRNAs in non-Hodgkin's lymphoma (NHL) radiosensitivity. Microarray was employed to compare the miRNA expression profiles in B cell lymphoma cell line Raji before and after a 2-Gy dose of radiation. A total of 20 differentially expressed miRNAs were identified including 10 up-regulated and 10 down-regulated (defined as P < 0.05). Among the differentially expressed miRNAs, miR-148b was up-regulated 1.53-fold in response to radiation treatment. A quantitative real-time polymerase chain reaction (PCR) assay confirmed the up-regulation of miR-148b after radiation. Transient transfection experiments showed that miR-148b was up-regulated by miR-148b mimic and down-regulated by miR-148b inhibitor in the Raji cells. A proliferation assay showed that miR-148b could inhibit the proliferation of Raji cells before and after radiation. A clonogenic assay demonstrated that miR-148b sensitized Raji cells to radiotherapy. MiR-148b did not affect the cell cycle profile of post-radiation Raji cells compared with controls. An apoptosis assay showed that miR-148b enhanced apoptosis of Raji cells after irradiation. Taken together, these results demonstrate that miR-148b increased the radiosensitivity of NHL cells probably by promoting radiation-induced apoptosis, which suggests that miR-148b plays an important role in the response of NHL to ionizing radiation.

MicroRNAs and Their Impact on Radiotherapy for Cancer

“…Induction of apoptosis, possibly mediated by inactivation of the PI3K-Akt pathway, can also be a result of miR-126 overexpression, and lead to enhanced radiosensitivity (22). In an irradiated non-Hodgkin's lymphoma cell line, miR-148b has been found to increase radiosensitivity of cells (67). In this context, radiation-induced apoptosis through repression of DNA methyltransferase 3b (DNMT3b) is a possible underlying mechanism (67).…”

“…In an irradiated non-Hodgkin's lymphoma cell line, miR-148b has been found to increase radiosensitivity of cells (67). In this context, radiation-induced apoptosis through repression of DNA methyltransferase 3b (DNMT3b) is a possible underlying mechanism (67). In addition, miR-181a targets another pro-apoptotic gene, PRKCD (protein kinase C delta type) and contributes to radioresistance by negative regulation of PRKCD expression and inhibition of radiation-induced apoptosis in cervical cancer cell lines (12).…”

microRNAs in Cancer Cell Response to Ionizing Radiation

“…As an example, miR-148b is induced by IR in non-Hodgkin's lymphoma, but repressed by IR in endothelial cells (139,152), demonstrating the variability in IR-induced expression changes. It is interesting to note that miRNA expression changes were not always consistent within a single cell line, specifically with regard to IR dose and recovery time post-IR.…”

Cell Survival Following Radiation Exposure Requires miR-525-3p Mediated Suppression of ARRB1 and TXN1

“…Modulation of specific miRNAs reveals they can have both pro- and anti-survival functions following exposure to radiation. Wu et al found that miR-148b expression was increased after radiation and enhanced the radiosensitivity of Non-Hodgkin Lymphoma cells by promoting apoptosis [21]. Similarly, the overexpression of let-7a decreased K-Ras expression and radiosensitized lung cancer cells [22], whilst increased miR-521 expression sensitized prostate cancer cells to radiation treatment through the regulation of the DNA repair protein CSA [16].…”