One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (FU)-based chemotherapy. Various reports showed that ectopic expression and function of microRNAs (miRNAs) played key roles to mediate apoptosis at the post-transcriptional level. To further explore the possible mechanisms, we evaluated the prognostic effect of miR-218 in patients with CRC receiving 5-FU-based treatment and investigated the proapoptotic role of miR-218 in vitro. Primary tumour specimens and adjacent non-tumour sites were used to determine miR-218 expression distribution and explore its potential prognostic value in response to 5-FU-based treatment in patients with CRC. HCT116 and HT29 cells were transfected with precursor miR-218 or negative control, followed by assays to investigate its influence on apoptosis, cell proliferation and pathways involved in molecular mechanisms of chemoresistance to 5-FU. Results showed that high miR-218 expression was associated with positive response to firstline 5-FU treatment in CRC patients. MiR-218 promoted apoptosis, inhibited cell proliferation and caused cell cycle arrest in CRC cells by suppressing BIRC5 expression. Furthermore, miR-218 enhanced 5-FU cytotoxicity in CRC cells by suppressing the 5-FU targeted enzyme, thymidylate synthase (TS). In conclusion, we demonstrated that high miR-218 expression had a positive prognostic value in 5-FU-based treatments for CRC patients and discovered a novel mechanism mediated by miR-218 to promote apoptosis and to function synergistically with 5-FU to promote chemosensitivity by suppressing BIRC5 and TS in CRC. These suggest the unique potential of miR-218 as a novel candidate for developing miR-218-based therapeutic strategies in CRC.

We report on the fabrication of a NO2 gas sensor from room-temperature reduction of graphene oxide(GO) via two-beam-laser interference (TBLI). The method of TBLI gives the distribution of periodic dissociation energies for oxygen functional groups, which are capable to reduce the graphene oxide to hierarchical graphene nanostructures, which holds great promise for gaseous molecular adsorption. The fabricated reduced graphene oxide(RGO) sensor enhanced sensing response in NO2 and accelerated response/recovery rates. It is seen that, for 20 ppm NO2, the response (Ra/Rg) of the sensor based on RGO hierarchical nanostructures is 1.27, which is higher than that of GO (1.06) and thermal reduced RGO (1.04). The response time and recovery time of the sensor based on laser reduced RGO are 10 s and 7 s, which are much shorter than those of GO (34 s and 45 s), indicating that the sensing performances for NO2 sensor at room temperature have been enhanced by introduction of nanostructures. This mask-free and large-area approach to the production of hierarchical graphene micro-nanostructures, could lead to the implementation of future graphene-based sensors.

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