MicroRNA expression profiles in human cancer cells after ionizing radiation

Abstract

IntroductionMicroRNAs are regulators of central cellular processes and are implicated in the pathogenesis and prognosis of human cancers. MicroRNAs also modulate responses to anti-cancer therapy. In the context of radiation oncology microRNAs were found to modulate cell death and proliferation after irradiation. However, changes in microRNA expression profiles in response to irradiation have not been comprehensively analyzed so far. The present study's intend is to present a broad screen of changes in microRNA expression following irradiation of different malignant cell lines.Materials and methods1100 microRNAs (Sanger miRBase release version 14.0) were analyzed in six malignant cell lines following irradiation with clinically relevant doses of 2.0 Gy. MicroRNA levels 6 hours after irradiation were compared to microRNA levels in non-irradiated cells using the "Geniom Biochip MPEA homo sapiens".ResultsHierarchical clustering analysis revealed a pattern, which significantly (p = 0.014) discerned irradiated from non-irradiated cells. The expression levels of a number of microRNAs known to be involved in the regulation of cellular processes like apoptosis, proliferation, invasion, local immune response and radioresistance (e. g. miR-1285, miR-24-1, miR-151-5p, let-7i) displayed 2 - 3-fold changes after irradiation. Moreover, several microRNAs previously not known to be radiation-responsive were discovered.ConclusionIonizing radiation induced significant changes in microRNA expression profiles in 3 glioma and 3 squamous cell carcinoma cell lines. The functional relevance of these changes is not addressed but should by analyzed by future work especially focusing on clinically relevant endpoints like radiation induced cell death, proliferation, migration and metastasis.

MicroRNAs and Their Impact on Radiotherapy for Cancer

“…Significantly, certain miRNAs have been identified to consistently show characteristic changes postirradiation across a range of different cancers. For example, expression of several members of the let-7 family, a well-known tumor suppressor and regulator of the K-Ras oncogene, were found to be affected by radiation exposure (29,30,(32)(33)(34)(35). Most members of the let-7 family (except let-7g) have been found to be downregulated in irradiated fibroblasts (33), lung cancer cells (30) or colon cancer cells (35).…”

“…Most members of the let-7 family (except let-7g) have been found to be downregulated in irradiated fibroblasts (33), lung cancer cells (30) or colon cancer cells (35). However, in irradiated glioma and squamous cell carcinoma cell lines REVIEW some members of the let-7 family are upregulated (29,34). Another two miRNAs, miR-21 and miR-34, are consistently upregulated in various benign and malignant cell lines after irradiation (28, 34, 36-38).…”

“…Niemoeller et al showed that radiation exposure led to 2-3-fold changes in the expression levels of various miRNAs, such as let-7i, miR-24-1, miR-151-5p and miR-1285 in different cancer cell lines (29). Significantly, certain miRNAs have been identified to consistently show characteristic changes postirradiation across a range of different cancers.…”

“…The majority of published studies have focused on (benign or malignant) cell lines or cancer tissue biopsies, and investigated whether radiation exposure is associated with characteristic changes to miRNA expression profiles (5,(27)(28)(29)(30)(31). In benign cells, miRNA expression has been shown to be significantly impacted by ionizing radiation (27,28).…”

A promising light for an impossible disease: miRNAs in malignant gliomas

“…Radioresistance adds another barrier to treatment efficiency in GBM. Not surprisingly, Niemoeller et al's ana lysis of human glioma cells demonstrated upregulation of miRNA clusters after treatment with clinically relevant radiation doses [19]. These results are somewhat expected as miRNAs can also be targets of molecular therapy, and those involved in apoptosis or regulating the expression of specific genes may induce the apoptosis of tumor cells exhibiting radioresistance [20].…”