Radiation therapy is one of the most common cancer treatments. It is important to understand how cells respond to ionizing radiation (IR) to improve therapeutic efficacy. Circular RNAs (circRNAs) recently have been found to regulate a variety of cellular processes. However, it is poorly defined that their expression pattern and their identity in cells following IR exposure. Here, we performed high-throughput sequencing and comprehensive analysis of circRNA expression in human embryonic kidney (HEK) 293T cells before and after irradiation. We identified totally 5592 circRNAs and discovered 1038 new circRNAs. We found 158 circRNAs with significantly differential expression after IR exposure. Among them, there were 61 upregulated and 97 downregulated circRNAs. Using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and circRNA-microRNAmessenger RNA network analyses, we found the differentially expressed circRNAs might be involved in the signal pathways of oxidative phosphorylation, epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, and mammalian target of rapamycin (mTOR) signaling.

Tissue and cell damage caused by ionizing radiation is often highly genotoxic. The swift repair of DNA damage is crucial for the maintenance of genomic stability and normal cell fitness. Long noncoding RNAs (lncRNAs) have been reported to play an important role in many physiological and pathological processes in cells. However, the exact function of lncRNAs in radiation-induced DNA damage has yet to be elucidated. Therefore, this study aimed to analyze the potential role of lncRNAs in radiation-induced DNA damage. We examined the expression profiles of lncRNAs and mRNAs in 293T cells with or without 8 Gy irradiation using high-throughput RNA sequencing. We then performed comprehensive transcriptomic and bioinformatic analyses of these sequencing results. A total of 18,990 lncRNAs and 16,080 mRNAs were detected in all samples. At 24 h post irradiation, 49 lncRNAs and 323 mRNAs were differentially expressed between the irradiation group and the control group. qRT-PCR was used to verify the altered expression of six lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the predicted genes were mainly involved in the histone mRNA metabolic process and Wnt signaling pathways. This study may provide novel insights for the study of lncRNAs in radiation-induced DNA damage.

No abstract

Mesenchymal stem cells (MSCs) derived from different tissues may aid in the regeneration of radiation-induced organ lesions; however, the radiation responses of human MSCs from different sources are unknown. In our study, a comparison of the results from cell proliferation, apoptosis, cell cycle, DNA damage, and DNA repair assays consistently showed that MSCs derived from adipose tissue possess a significantly stronger radiation resistance capacity than MSCs derived from umbilical cord and gingival, which is accompanied by a higher level of phosphorylated signal transducer and activator of transcription 3 (Stat3) expression. This reminds us Stat3 could be a potential biomarker of radiation resistance. These findings provide a better understanding of radiation-induced biologic responses in MSCs and may lead to the development of better strategies for stem cell treatment and cancer therapy.

No abstract

No abstract

RMI1 (RecQ-mediated genome instability protein 1) forms a conserved BTR complex with BLM, Topo IIIα, and RMI2, and its absence causes genome instability. It has been revealed that RMI1 localizes to nuclear foci with BLM and Topo IIIα in response to replication stress, and that RMI1 functions downstream of BLM in promoting replication elongation. However, the precise functions of RMI1 during replication stress are not completely understood. Here we report that RMI1 knockdown cells are hypersensitive to hydroxyurea (HU). Using comet assay, we show that RMI1 knockdown cells exhibit accumulation of broken DNAs after being released from HU treatment. Moreover, we demonstrate that RMI1 facilitates the recovery from activated checkpoint and resuming the cell cycle after replicative stress. Surprisingly, loss of RMI1 results in a failure of RAD51 loading onto DNA damage sites. These findings reveal the importance of RMI1 in response to replication stress, which could explain the molecular basis for its function in maintaining genome integrity.

Accumulating evidence has shown that long non-coding RNAs (lncRNAs) play significant roles in the development and progression of many types of cancer including colorectal cancer. RP11-400N13.3 is a novel lncRNA discovered recently and its biological function and underlying mechanism in colorectal cancer remain elusive. This study aimed to reveal the relationship between RP11-400N13.3 and colorectal cancer. Our results demonstrated that the expression of RP11-400N13.3 was significantly upregulated in both colorectal cancer tissues and cell lines as compared to normal adjacent tissues and normal colonic epithelial cells by RT-qPCR, respectively. Upregulation of RP11-400N13.3 was found to be correlated with a poor overall survival rate. Functional studies revealed that RP11-400N13.3 facilitated the proliferation, migration, invasion and tumor growth of colorectal cancer cells while inhibiting the apoptosis of cancer cells in vitro and in vivo. We also observed that RP11-400N13.3 serves as a sponge for miR-4722-3p, and that P2Y receptor family member 8 (P2RY8) was predicted to be a target of miR-4722-3p by bioinformatics analysis. Western blot assay indicated that the expression of P2RY8 was negatively or positively regulated by miR-4722-3p or RP11-400N13.3. In addition, rescue experiments revealed that RP11-400N13.3 promoted proliferation, migration and invasion by directly regulating the expression of miR-4722-3p and P2RY8. In conclusion, our results revealed that RP11-400N13.3 promoted colorectal cancer progression via modulating the miR-4722-3p/P2RY8 axis, thus suggesting RP11-400N13.3 as a potential therapeutic target for the treatment of colorectal cancer.