Human exposure to low dose ionizing radiation affects miR-21 and miR-625 expression levels.

BACKGROUND: Recently exposure to ionizing radiation driven by artificial radiation sources such as Medical X-rays and Nuclear medicine has increased hastily. Ionizing radiation-induced the DNA damage and activate the DNA damage response signaling pathways. The aim of this study was to evaluate the role of miR-21 and miR-625 in response to low-dose ionizing radiation. MATERIALS AND METHODS: In this study, the blood sample of 38 volunteer patients who underwent Cardiac scans before and after 99mTc-MIBI injection were used. The WBC of patients was used for RNA extraction and after cDNA synthesis by the poly-A method the expression level of miR-21 and miR-625 was evaluated by real-time PCR method. RESULTS: The results of this study indicated that miR-21 and miR- 625 were significantly upregulated under exposure to low-dose ionizing radiation. The expression level of these miRNAs was not significantly correlated with the age and BMI of patients. More ever the bioinformatics analysis indicated that SP1 was a common target of both miRNAs and had the highest degree between hub genes. CONCLUSION: In summary miR-21 and miR-625 can contribute to the response to acute low dose ionizing radiation by targeting the SP1. However further studies should be carried out on the molecular mechanism of effects of miR-21 and miR-625 in response to low dose ionizing radiation by targeting the SP1.

miR­182­5p contributes to radioresistance in nasopharyngeal carcinoma by regulating BNIP3 expression.

Radioresistance is the primary roadblock limiting the success of treatment of nasopharyngeal carcinoma (NPC). microRNA (miRNA/miR)­182­5p has been reported to affect the sensitivity of cancer cells to irradiation; however, the role of miR­182­5p in NPC has not been assessed. The aim of the present study was to investigate the contribution of miR­182­5p to the radioresistance of NPC cells. The key mRNA and miRNA involved in NPC radioresistance were identified using bioinformatics analysis. The two cell lines used in the present study were 5­8F cells (radio­sensitive) and 5­8F­R cells (radioresistant). A dual­luciferase reporter assay system was used to validate the binding between BCL2/adenovirus E1B 19 kDa protein­interacting protein 3 (BNIP3) mRNA and miR­182­5p. Reverse transcription­quantitative PCR and western blotting were used to determine the RNA and protein expression levels. To obtain a deeper insight into the effects of the BNIP3/miR­182­5p axis on NPC radioresistance, Cell Counting Kit­8, wound healing, Transwell invasion and colony formation assays, as well as flow cytometry analysis were performed. The results showed that miR­182­5p and BNIP3 were up and downregulated, respectively, in 5­8F­R cells. BNIP3 was also confirmed to be the target of miR­182­5p, and miR­182­5p reversed the inhibitory effect of BNIP3 in 5­8F­R cells. The cellular experiments showed that upregulation of BNIP3 not only inhibited cell proliferation, viability, invasion and migration, but also promoted the apoptosis of 5­8F­R cells. However, the effects of BNIP3 were attenuated by the simultaneous upregulation of miR­182­5p. Thus, through downregulation of BNIP3, miR­182­5p contributed to radiation resistance of NPC cells.

RWR-algorithm-based dissection of microRNA-506-3p and microRNA-140-5p as radiosensitive biomarkers in colorectal cancer.

Radiotherapy resistance is one of the main causes for treatment failure in colorectal cancer (CRC), and it is associated with the deregulation of certain microRNAs. In this study, we constructed the microRNA-mRNA network consisting of 2275 microRNAs and 7045 target genes, collected the known microRNAs related to CRC-radiosensitivity (CRCR) (n=18) as the seed nodes, and applied the algorithm of random walk with restart (RWR) to the network to identify novel CRCR-related microRNAs (n=263). In functional analysis, 263 novel microRNAs shared a high proportion of the same biological processes and pathways with the known microRNAs. In topological analysis of the sub-network of the 263 microRNAs and their targets, hsa-mir-506-3p and hsa-mir-140-5p were identified as network hub nodes. In plasma, radiosensitive patients had a higher expression level of hsa-mir-506-3p and hsa-mir-140-5p than radioresistant patients. In experimental validation, both hsa-mir-506-3p and hsa-mir-140-5p over-expression could obviously decrease the cell proliferation, survival rate and colonality in CRC cells after radiation. In conclusion, this study combined the novel network-based method with experimental validation, and identified two novel radiosensitive biomarkers of hsa-mir-506-3p and hsa-mir-140-5p in CRC.

MicroRNAs Responding to Space Radiation.

High-energy and high-atom-number (HZE) space radiation poses an inevitable potential threat to astronauts on deep space exploration missions. Compared with low-LET radiation, high-energy and high-LET radiation in space is more efficient in inducing clustered DNA damage with more serious biological consequences, such as carcinogenesis, central nervous system injury and degenerative disease. Space radiation also causes epigenetic changes in addition to inducing damage at the DNA level. Considering the important roles of microRNAs in the regulation of biological responses of radiation, we systematically reviewed both expression profiling and functional studies relating to microRNAs responding to space radiation as well as to space compound environment. Finally, the directions for improvement of the research related to microRNAs responding to space radiation are proposed. A better understanding of the functions and underlying mechanisms of the microRNAs responding to space radiation is of significance to both space radiation risk assessment and therapy development for lesions caused by space radiation.

Effects of Amifostine Pre-treatment on MIRNA, LNCRNA, and MRNA Profiles in the Hypothalamus of Mice Exposed to 60Co Gamma Radiation.

There is increasing evidence that the expression of non-coding RNA and mRNA (messenger RNA) is significantly altered following high-dose ionizing radiation (IR), and their expression may play a critical role in cellular responses to IR. However, the role of non-coding RNA and mRNA in radiation protection, especially in the nervous system, remains unknown. In this study, microarray profiles were used to determine microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in the hypothalamus of mice that were pretreated with amifostine and subsequently exposed to high-dose IR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We found that fewer miRNAs, lncRNAs, and mRNAs were induced by amifostine pre-treatment in exposed mice, which exhibited antagonistic effects compared to IR, indicating that amifostine attenuated the IR-induced effects on RNA profiles. GO and KEGG pathway analyses showed changes in a variety of signaling pathways involved in inflammatory responses during radioprotection following amifostine pre-treatment in exposed mice. Taken together, our study revealed that amifostine treatment altered or attenuated miRNA, lncRNA, and mRNA expression in the hypothalamus of exposed mice. These data provide a resource to further elucidate the mechanisms underlying amifostine-mediated radioprotection in the hypothalamus.

Differential regulation of microRNA-15a by radiation affects angiogenesis and tumor growth via modulation of acid sphingomyelinase.

Activation of acid sphingomyelinase (SMPD1) and the generation of ceramide is a critical regulator of apoptosis in response to cellular stress including radiation. Endothelial SMPD1 has been shown to regulate tumor responses to radiation therapy. We show here that the SMPD1 gene is regulated by a microRNA (miR), miR-15a, in endothelial cells (ECs). Standard low dose radiation (2 Gy) upregulates miR-15a and decreases SMPD1 levels. In contrast, high dose radiation (10 Gy and above) decreases miR-15a and increases SMPD1. Ectopic expression of miR-15a decreases both mRNA and protein levels of SMPD1. Mimicking the effects of high dose radiation with a miR-15a inhibitor decreases cell proliferation and increases active Caspase-3 & 7. Mechanistically, inhibition of miR-15a increases inflammatory cytokines, activates caspase-1 inflammasome and increases Gasdermin D, an effector of pyroptosis. Importantly, both systemic and vascular-targeted delivery of miR-15a inhibitor decreases angiogenesis and tumor growth in a CT26 murine colorectal carcinoma model. Taken together, our findings highlight a novel role for miR mediated regulation of SMPD1 during radiation responses and establish proof-of-concept that this pathway can be targeted with a miR inhibitor.

Effect of simulated microgravity and ionizing radiation on expression profiles of miRNA, lncRNA, and mRNA in human lymphoblastoid cells.

In space, multiple unique environmental factors, particularly microgravity and space radiation, pose a constant threat to astronaut health. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are functional RNAs that play critical roles in regulating multiple cellular processes. To gain insight into the role of non-coding RNAs in response to radiation and microgravity, we analyzed RNA expression profiles in human lymphoblastoid TK6 cells incubated for 24 h under static or rotating conditions to stimulate microgravity in space, after 2-Gy γ-ray irradiation. The expression of 14 lncRNAs and 17 mRNAs (differentially-expressed genes, DEGs) was found to be significantly downregulated under simulated microgravity conditions. In contrast, irradiation upregulated 55 lncRNAs and 56 DEGs, whereas only one lncRNA, but no DEGs, was downregulated. Furthermore, two miRNAs, 70 lncRNAs, and 87 DEGs showed significantly altered expression in response to simulated microgravity after irradiation, and these changes were independently induced by irradiation and simulated microgravity. GO enrichment and KEGG pathway analyses indicated that the associated target genes showed similar patterns to the noncoding RNAs and were suggested to be involved in the immune/inflammatory response including LPS/TLR, TNF, and NF-κB signaling pathways. However, synergistic effects on RNA expression and cellular responses were also observed with a combination of simulated microgravity and irradiation based on microarray and RT-PCR analysis. Together, our results indicate that simulated microgravity and irradiation additively alter expression patterns but synergistically modulate the expression levels of RNAs and their target genes in human lymphoblastoid cells.

Radiation Therapy Reduced Blood Levels of LDH, HIF-1α, and miR-210 in OSCC.

Radiation Therapy (RT) is a treatment option for a large number of neoplasias. However, the effect of RT on the level of hypoxia markers is poorly understood. The present study aimed to investigate the effect of RT on the levels of hypoxic markers in Oral squamous cell carcinoma (OSCC). Evaluation of HIF-1α and miR-210 levels in OSCC was performed. Then a proteomic analysis was performed to identify candidate hypoxic targets of RT. To validate proteomic studies, the effect of RT on HIF-1α, miR-210, PDH-A and LDH-A levels under hypoxia was assessed by qRT-PCR. The impact of RT in hypoxia markers was evaluated in patients to confirm in vitro results. An increase in the HIF-1α levels was observed in OSCC. RT reduced OSCC cell proliferation and migration. Interestingly, hypoxia could revert the effect of radiation on OSCC phenotype. However, proteomics analyses suggested that LDH is one of the critical targets of RT even in hypoxia. Moreover, RT decreased HIF-1α, miR-210, and LDH even in hypoxia. The current study demonstrated that hypoxia could revert the effects of RT in the OSCC context. However, RT reduces the levels HIF-1α, miR-210 and LDH in vivo and in vitro. The consequences of RT in blood should be carefully investigated.

Competing endogenous network analysis identifies lncRNA Meg3 activates inflammatory damage in UVB induced murine skin lesion by sponging miR-93-5p/epiregulin axis.

In this study, we obtained the RNA expression data of murine skin tissues of control, and UVB irradiated groups. After the re-annotation of lncRNAs, a gene expression similarity analysis was done by WGCNA. The target mRNA prediction of lncRNAs, miRNAs, and ceRNA regulatory networks were constructed by five lncRNAs, 14 miRNAs and 54 mRNAs, respectively. Based on the ceRNA network of UVB-induced skin lesions, it was evident that the dysregulation of Meg3 has critical effects on the UVB-induced inflammatory lesion of murine skin tissues. The overexpression of Meg3 after UVB irradiation was observed in primary murine skin fibroblasts, and the up-regulated Meg3 expression was related to the activation of the inflammatory cytokines. These functional experiments demonstrated that the RNA silencing of Meg3 in murine skin fibroblasts could suppress the expression of the cytokines (in vitro) and UVB-induced skin lesions (in vivo). Moreover, the Meg3 functioned as a competing endogenous RNA (ceRNA) that acted as a sponge for miR-93-5p and thereby modulated the expression of Epiregulin (Ereg). Our results proved that Meg3 was involved in UVB-induced skin inflammation and that the ceRNA networks, which includes miR-93-5p and Ereg, could prove to be a potential therapeutic target for UVB-induced skin damage.

COMPREHENSIVE EXPRESSION ANALYSIS OF MIRNAS IN MICE EXPOSED TO LETHAL RADIATION AND/OR RADIO-MITIGATIVE DRUG.

New minimally invasive indicators that are capable of predicting the biological effects and radiation damage to various organs and systems are urgently needed for the development of optimal treatment protocols for victims of radiation accidents. In the present study, we focused on microRNA (miRNA) that have recently emerged as biomarkers for predicting and diagnosing various pathological conditions and identified the serum miRNA signatures. All of the mice treated with lethal radiation alone strongly expressed certain serum miRNAs detectable for 24 h after radiation exposure, whereas the administration of radio-mitigative drug immediately after irradiation suppressed these miRNA expressions to the same levels as in control mice. These results suggest that serum miRNAs may reflect the degree of radiation damage and can be used to predict the radiation-mitigative information in victims of accidental radiation exposure.

Effect of Radiation on the Expression of CVD-related miRNAs, Inflammation and Endothelial Dysfunction of HUVECs.

BACKGROUND/AIM: Radiotherapy (RT) can lead to cardiovascular disease (CVD). Evidence suggests that radiation modulates miRNA levels. Our purpose was to assess the acute response to radiation-induced modulation of the expression of miRNA-146a, miRNA-155, miRNA-221, and miRNA-222, inflammatory response and endothelial dysfunction on endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 2 Gy RT, and intracellular levels of selected miRNAs were measured by real-time polymerase chain reaction at 2 and 24 h. Cytokine and adhesion molecule release were also assessed. RESULTS: Results showed that 2 Gy significantly increased the expression of miRNA-221 and miRNA-222, and reduced the level of miRNA-155 after 2 h; whereas miRNA-146a and miRNA-155 were significantly overexpressed and miRNA-222 was significantly down-regulated at 24 h. Interleukin-8 and soluble vascular cell adhesion molecule 1 levels were not affected by the studied RT. CONCLUSION: RT at 2 Gy modulated expression of selected miRNAs by endothelial cells after 2 and 24 h, which might be related to CVD development in patients who receive RT.

BIOINFORMATIC ANALYSIS OF DOSE- AND TIME-DEPENDENT miRNome RESPONSES.

The advent of new 'omics' techniques determined a massive boost in the measurement of the whole spectra of molecules within cells, favoring promising new radiobiological studies at low doses. The main aim of this work was to assess the radiation-induced perturbations of miRNA profiles and their temporal dynamics. Human Umbilical Vein Endothelial Cells were irradiated with low doses of γ-rays. At different time points post-irradiation, cells were harvested and miRNAs isolated. A full mapping of the miRNA sequences via Next-Generation-Sequencing analysis was performed followed by bioinformatic analyses. Pathway enrichment analyses on the differentially expressed miRNAs focused both on the averaged effects of different doses over the 24-h experiment and on the altered temporal dynamics of the miRNA profiles. These complementary analyses provided a picture of the dose- and time-dependent miRNAs responses, allowing to better explore the candidate biomarkers linked to radiation exposures and their corresponding pathways and functions.

Regulation through MicroRNAs in Response to Low-Energy N+ Ion Irradiation in Oryza sativa.

MicroRNAs (miRNAs) are a non-coding regulatory RNAs that play significant roles in plant growth and development, especially in the stress response. Low-energy ion radiation, a type of environmental stress, can cause multiple biological effects. To understand the roles of miRNAs in response to low-energy N+ ion radiation in Oryza sativa, high-throughput sequencing of small RNAs was carried out to detect the expression of miRNAs in the shoots of the rice after 2 × 1017 N+/cm2 irradiation. The differentially expressed 28 known miRNAs were identified, 17 of these identified miRNAs were validated by real-time quantitative fluorescent PCR (q-PCR), including 9 up-regulated miRNAs (miR1320-3p, miR1320-5p, miR156b-3p, miR156c-5p, miR156c-3p/g-3p, miR1561-5p, miR398b and miR6250) and 8 down-regulated miRNAs (miR156a/e/i, miR156k, miR160f-5p, miR166j-5p, miR1846e and miR399d). In addition, 45 novel radiationresponsive miRNAs were predicted, and 8 of them were verified by q-PCR. The target genes of radiation-responsive miRNAs were predicted and gene function enrichment analysis was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of 9 targets of 4 known miRNA families (miR156, miR399, miR1320 and miR398) and 2 targets of 2 novel miRNAs were quantified by q-PCR, and a strong negative regulation relation between miRNAs and their targets were observed. Those targets including SQUAMOSA promoterbinding-like protein (SPL) genes, copper/zinc superoxide dismutase (Cu/Zn-SOD), copper chaperone for SOD (CCS1) and electron transporter/ heat-shock protein binding protein (HSP), which are involved in growth and defense against various stresses, especially associated with reactive oxygen species (ROS) scavenging. This work provides important information for understanding the ROS generation and elimination mechanisms closely related to miRNAs in rice seedlings after low-energy N+ radiation exposure.

MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma.

BACKGROUND: Glioma is the most prevalent malignant tumor in human central nervous systems. Recently, the development of resistance to radiotherapy in glioma patients markedly vitiates the therapy outcome. MiR-153-3p has been reported to be closely correlated with tumor progression, but its effect and molecular mechanism underlying radioresistance remains unclear in glioma. METHODS: The expression of miR-153-3p was determined in radioresistant glioma clinical specimens as well as glioma cell lines exposed to irradiation (IR) using quantitative real-time PCR. Cell viability, proliferation and apoptosis were then evaluated by MTT assay, colony formation assay, Flow cytometry analysis and caspase-3 activity assay in glioma cells (U87 and U251). Tumor forming was evaluated by nude mice model in vivo. TUNEL staining was used to detect cell apoptosis in nude mice model. The target genes of miR-153-3p were predicted and validated using integrated bioinformatics analysis and a luciferase reporter assay. RESULTS: Here, we found that miR-153-3p was down-regulated in radioresistant glioma clinical specimens as well as glioma cell lines (U87 and U251) exposed to IR. Enhanced expression of miR-153-3p promoted the radiosensitivity, promoted apoptosis and elevated caspase-3 activity in glioma cells in vitro, as well as the radiosensitivity in U251 cell mouse xenografs in vivo. Mechanically, B cell lymphoma-2 gene (BCL2) was identified as the direct and functional target of miR-153-3p. Moreover, restoration of BCL2 expression reversed miR-153-3p-induced increase of radiosensitivity, apoptosis and caspase-3 activity in U251 cells in vitro. In addition, clinical data indicated that the expression of miR-153-3p was significantly negatively associated with BCL2 in radioresistance of glioma samples. CONCLUSIONS: Our findings suggest that miR-153-3p is a potential target to enhance the effect of radiosensitivity on glioma cells, thus representing a new potential therapeutic target for glioma.

Analysis of changes to lncRNAs and their target mRNAs in murine jejunum after radiation treatment.

LncRNAs have been reported to play an important role in various diseases. However, their role in the radiation-induced intestinal injury is unknown. The goal of the present study was to analyse the potential mechanistic role of lncRNAs in the radiation-induced intestinal injury. Mice were divided into two groups: Control (non-irradiated) and irradiated. Irradiated mice were administered 14 Gy of abdominal irradiation (ABI) and were assessed 3.5 days after irradiation. Changes to the jejuna of ABI mice were analysed using RNA-Seq for alterations to both lncRNA and mRNA. These results were validated using qRT-PCR. LncRNAs targets were predicted based on analysis of lncRNAs-miRNAs-mRNAs interaction. 29 007 lncRNAs and 17 142 mRNAs were detected in the two groups. At 3.5 days post-irradiation, 91 lncRNAs and 57 lncRNAs were significantly up- and downregulated respectively. Similarly, 752 mRNAs and 400 mRNAs were significantly up- and downregulated respectively. qRT-PCR was used to verify the altered expression of four lncRNAs (ENSMUST00000173070, AK157361, AK083183, AK038898) and four mRNAs (Mboat1, Nek10, Ccl24, Cyp2c55). Gene ontology and KEGG pathway analyses indicated the predicted genes were mainly involved in the VEGF signalling pathway. This study reveals that the expression of lncRNAs was altered in the jejuna of mice post-irradiation. Moreover, it provides a resource for the study of lncRNAs in the radiation-induced intestinal injury.

Correlation study between long non-coding RNA MALAT1 and radiotherapy efficiency on cervical carcinoma and generation of radiotherapy resistant model of cancer.

OBJECTIVE: This study aims to construct a radiotherapy model on cervical carcinoma cells and to illustrate the correlation between long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) and radiotherapy efficiency. PATIENTS AND METHODS: A total of 60 cervical carcinoma patients were recruited, and quantitative PCR (qPCR) was employed to detect MALAT1 expression. A dosage-time curve helped to construct radiotherapy resistant model on cervical carcinoma cell CaSki. Lentivirus transfection was used to silence MALAT1 expression, followed by quantification of clonal formation, apoptosis, and cycle after combined radiotherapy. Bioinformatics tool (miRcode.org), reporter gene and qPCR were used to predict microRNA (miR) interaction with MALAT1. By combining MALAT1 silencing, miR over-expression and radiotherapy, effects on the cervical cancer cell clonal formation, apoptosis, and cycle were observed. RESULTS: Comparing to radiotherapy sensitive tissues, the MALAT1 level was significantly elevated in radiotherapy resistant tissues (0.52 ± 0.18 vs. 1.29 ± 0.34, p<0.05). MALAT1 expression in cervical carcinoma cell CaSki was further elevated with elongated radiation time and dosage (p<0.05). Comparing to controlled cells, MALAT1 silencing decreased viable cell percentage, enhanced apoptosis, increased G1 phase cells, and decreased G2/M ratio. Bioinformatics, reporter gene, and qPCR showed that MALAT1 exerted its roles in cervical carcinoma cells via interacting with miR-143, both of which had a significant correlation (r=0.77, p<0.01). MALAT1 silencing combined with miR-143 plus radiotherapy decreased viable cell percentage, enhanced apoptosis, increased G1 phase ratio, and decreased S or G2/M cells. CONCLUSIONS: In cervical carcinoma, MALAT1 can interact with miR-143 to modulate tumor cell survival, apoptosis and cell cycle, thus affecting radiotherapy efficiency.

Effects of microwave on extracellular vesicles and microRNA in milk.

This study demonstrates the effects of microwaves on the microRNA (miRNA) content of milk and milk extracellular vesicles (EV). We determined the miRNA concentration in milk subjected to different treatments using real-time PCR and a spectrophotometer. The miRNA expression and total RNA content of the microwaved milk samples were lower when compared with untreated milk. We measured the microstructure and the size distribution by scanning electron microscopy and dynamic light scattering to verify the loss of miRNA in microwaved milk due to damage to the EV. The results revealed that 2 different-sized EV were present and had an average size of 147.50 and 22.14 nm, respectively. Furthermore, acridine orange staining showed that the total RNA content in microwaved milk EV was lower than that in cow milk. These results suggest that EV may confer the protection and the stability of the miRNA in milk.

Ionizing Radiation Deregulates the MicroRNA Expression Profile in Differentiated Thyroid Cells.

BACKGROUND: Ionizing radiation (IR) is a well-known risk factor for papillary thyroid cancer, and it has been reported to deregulate microRNA expression, which is important to thyroid carcinogenesis. Therefore, this study investigated the impact of IR on microRNA expression profile of the normal thyroid cell line (FRTL-5 CL2), as well as its effect on radiosensitivity of thyroid cancer cell lines, especially the human anaplastic thyroid carcinoma cell line (8505c). METHODS: The global microRNA expression profile of irradiated FRTL-5 CL2 cells (5 Gy X-ray) was characterized, and data were confirmed by quantitative real-time polymerase chain reaction evaluating the expression of rno-miR-10b-5p, rno-miR-33-5p, rno-miR-128-1-5p, rno-miR-199a-3p, rno-miR-296-5p, rno-miR-328a-3p, and rno-miR-541-5p in irradiated cells. The miR-199a-3p and miR-10b-5p targets were validated by quantitative real-time polymerase chain reaction, Western blot, and luciferase target assays. The effects of miR-199a-3p and miR-10b-5p on DNA repair were determined by evaluating the activation of the protein kinases ataxia-telangiectasia mutated, ataxia telangiectasia, and Rad3-related and the serine 39 phosphorylation of variant histone H2AX as an indirect measure of double-strand DNA breaks in irradiated FRTL-5 CL2 cells. The impact of miR-10b-5p on radiosensitivity was analyzed by cell counting and MTT assays in FRTL-5 CL2, Kras-transformed FRTL-5 CL2 (FRTL KiKi), and 8505c cell lines. RESULTS: The results reveal that miR-10b-5p and miR-199a-3p display the most pronounced alterations in expression in irradiated FRTL-5 CL2 cells. Dicer1 and Lin28b were validated as targets of miR-10b-5p and miR-199a-3p, respectively. Functional studies demonstrate that miR-10b-5p increases the growth rate of FRTL-5 CL2 cells, while miR-199a-3p inhibits their proliferation. Moreover, both of these microRNAs negatively affect homologous recombination repair, reducing activated ataxia-telangiectasia mutated and Rad3-related protein levels, consequently leading to an accumulation of the serine 39 phosphorylation of variant histone H2AX. Interestingly, the overexpression of miR-10b-5p decreases the viability of the irradiated FRTL5-CL2 and 8505c cell lines. Consistent with this observation, its inhibition in FRTL KiKi cells, which display high basal expression levels of miR-10b-5p, leads to the opposite effect. CONCLUSIONS: These results demonstrate that IR deregulates microRNA expression, affecting the double-strand DNA breaks repair efficiency of irradiated thyroid cells, and suggest that miR-10b-5p overexpression may be an innovative approach for anaplastic thyroid cancer therapy by increasing cancer cell radiosensitivity.