Circular Sponge Research Articles

Circular Sponge against miR-21 Enhances the Antitumor Activity of Doxorubicin against Breast Cancer Cells

Breast cancer is the most common type of cancer in women, with chemotherapy being the main strategy. However, its effectiveness is reduced by drug resistance mechanisms. miR-21 is upregulated in breast cancer that has been linked to drug resistance and carcinogenic processes. Our aim was to capture miR-21 with a circular sponge (Circ-21) and thus inhibit the carcinogenic processes and drug resistance mechanisms in which it participates. Proliferation, migration, colony formation, cell cycle, and poly [ADP-ribose] polymerase 1 (PARP-1) and vascular endothelial growth factor (VEGF) detection assays were performed with MCF7 breast cancer cells and MCF10A non-tumor cells. In addition, doxorubicin resistance tests and detection of drug resistance gene expression were performed in MCF7 cells. Reduction in proliferation, as well as migration and colony formation, increased PARP-1 expression, inhibition of VEGF expression and cell cycle arrest in G2/M phase were displayed in the Circ-21 MCF7, which were not observed in the MCF10A cells. Furthermore, in the MCF7 cells, the Circ-21 enhanced the antitumor activity of doxorubicin and decreased the expression of resistance genes: ABCA1, ABCC4, and ABCC5. Based on these results, the use of Circ-21 can be considered a first step for the establishment of an effective gene therapy in the treatment of breast cancer.

Synthetic Circular miR-21 Sponge as Tool for Lung Cancer Treatment.

Lung cancer is the most common cancer in the world and several miRNAs are associated with it. MiRNA sponges are presented as tools to inhibit miRNAs. We designed a system to capture miRNAs based on circular RNAs (circRNA). To demonstrate its usefulness, we chose miR-21, which is upregulated and implicated in lung cancer. We constructed a miR-21 sponge and inserted it into a vector that facilitates circular RNA production (Circ-21) to study its effect on growth, colony formation, and migration in lung cancer cell lines and multicellular tumor spheroids (MTS). Circ-21 induced a significant and time-dependent decrease in the growth of A549 and LL2 cells, but not in L132 cells. Furthermore, A549 and LL2 cells transfected with Circ-21 showed a lower number of colonies and migration than L132. Similar findings were seen in A549 and LL2 Circ-21 MTS, which showed a significant decrease in volume growth, but not in L132 Circ-21 MTS. Based on this, the miR-21 circular sponge may suppress the processes of tumorigenesis and progression. Therefore, our system based on circular sponges seems to be effective, as a tool for the capture of other miRNAs.

Synthetic circular multi-miR sponge simultaneously inhibits miR-21 and miR-93 in esophageal carcinoma

MicroRNAs (miRs) are post-transcriptional regulators involved in the initiation and progression of many tumors. Recently, naturally occurring circular RNAs (circRNAs) have been described in eukaryotic cells:;they comprise a new class of gene regulators. Naturally occurring circular miR sponges, which induce miR loss-of-function, can prevent endogenous onco-miRs from binding to their cognate mRNA targets. These findings suggest that synthetic (artificial) circular RNAs could be constructed as therapeutic molecular sponges to suppress harmful onco-miRs. Using enzymatic ligation, we designed and constructed a circular RNA containing both miR-21 and miR-93 binding sites. The synthetic circular sponge was resistant to digestion with RNase R. Luciferase assays and functional experiments showed that the circular multi-miR sponge was more stable than its linear counterpart. Moreover, endogenous miR-21 and miR-93 were inhibited by the circular sponge. In addition, the synthetic sponge significantly suppressed cellular proliferation and migration while promoting apoptosis in esophageal carcinoma cells. Finally, in a murine xenograft model, the circular sponge significantly inhibited tumor growth in vivo. Taken together, these findings establish that the design and construction of efficient artificial miR sponges represent a novel strategy to achieve miR loss-of-function in molecular cancer therapeutics.

P108. Effects of 10 Hz tACS on phonological language processing

Introduction A previous study ( Hartwigsen et al., 2010 ) has shown that 10 Hz rTMS of the left or right posterior inferior frontal gyrus (IFG) impaired performance in a phonological decision-making task. However, it is unclear whether the neurodisruptive effect of 10 Hz-rTMS is caused by entrainment of alpha-oscillations. To address this issue, the present study investigated the following questions: (1) Are alpha-oscillations in the IFG functionally relevant for phonological processing? (2) Can we enhance alpha activity in the IFG using 10 Hz tACS? and (3) Does enhancement of alpha activity cause behavioral disruption? Methods 24 right-handed, healthy participants (12 male, age range: 18–30 years, mean = 21.96, SD = 3.36) participated in the study. 9 mm2 circular sponge electrodes were placed over the bilateral IFG. In three separate sessions, 1 mA tACS at 10 Hz or 16.18 Hz or sham stimulation were applied for 20 min. Before and after stimulation, 5 min of resting state EEG was recorded. The phonological task required the subjects to indicate via button press whether highly frequent German nouns like ‘Zebra’ consisted of two or three syllables. In a simple control task, participants had to indicate whether an arrow pointed left or right to control for unspecific effects. Results (1) Stimulation was a significant predictor for decision speed in the phonological task (p = .02). Specifically, participants responded faster after 10 Hz relative to sham stimulation, but not after 16.18 Hz. (2) This effect was task specific as tACS did not significantly affect the control task (p = 0.43). (3) Participants had an increase in resting state alpha power (p = .004), which wasn’t modulated by stimulation (p = .70). (4) We found a significant event related desynchronization in the alpha band (p Conclusion The results show an improvement in a phonological word task after applying 10 Hz tACS over the bilateral IFG but not in simple motoric control task. This might be explained by a paradoxical facilitation effect, resulting in an ‘optimal’ level of noise for task processing ( Miniussi et al., 2013 ) or by inhibition of surrounding areas that might be competing for task resources. Since no specific effect on alpha oscillations could be found, further studies will therefore investigate effects of focal online stimulation.

A Mesoporous ZSM-5 Zeolite Synthetized by a Novel Double Long-Alkyl-Chain Organosilane Template

Abstract A ZSM-5 zeolite molecular sieve was prepared by using a new type of double long-alkyl-chain organosilane template. The structure of the acquired zeolite was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption–desorption measurement, which showed a piled circular sponge crystal morphology and contained mesopores around 4 nm in it.