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Orofacial neuropathic pain is a common symptom induced by orofacial nerve injury caused by a range of trauma or dental and maxillofacial procedures but lacks effective treatment. Circular RNAs (circRNAs) participate in the regulatory processes of neuropathic pain. Nevertheless, the biological roles of circRNAs in orofacial neuropathic pain remain unexplored. In this study, circRNA sequencing and Real‐time quantitative polymerase chain reaction (RT‐qPCR) were carried out. Notably, a novel circRNA named circ_lrrc49 was identified to be downregulated following chronic constriction injury of the infraorbital nerve (CCI‐ION) in mice on day 14. Subsequent RNA Antisense Purification (RAP)‐mass spectrometry and RNA immunoprecipitation found a direct interaction between circ_lrrc49 and increased sodium tolerance 1 homolog (Ist1). Western blot (WB) identified decreased expression of Ist1 on day 14 post‐CCI‐ION. Considering the known relationship between Ist1 and autophagy, LC3‐II and p62 were detected to be upregulated, and an accumulation of autophagosomes were observed at the same time point. Besides, the knockdown of circ_lrrc49 by small interfering RNA (siRNA) reduced Ist1 expression, increased LC3‐II, p62 levels and autophagosomes amount, and evoked orofacial mechanical hypersensitivity, which could be counteracted by the Ist1 overexpression. Similarly, the knockdown of Ist1 by siRNA also increased LC3‐II and p62 levels and evoked orofacial mechanical hypersensitivity without influence on circ_lrrc49. Moreover, autophagy activation by rapamycin alleviated orofacial mechanical hypersensitivity evoked by CCI‐ION or circ_lrrc49 knockdown. In conclusion, our data revealed the existence of a circ_lrrc49/Ist1/autophagy signaling axis contributing to the progression of orofacial neuropathic pain. These discoveries reveal the intricate molecular processes that drive orofacial neuropathic pain and identify circ_lrrc49 as a promising target for potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

The anti-EGFR antibody cetuximab is used as a first-line targeted therapeutic drug in colorectal cancer. It has previously been reported that the efficacy of the EGFR antibody cetuximab is limited by the emergence of acquired drug resistance. In our previous study the transmissibility effect of exosomes from drug resistant tumor cells to sensitive tumor cells was identified. It can therefore be hypothesized that drug resistant cells might affect neighboring and distant cells via regulation of exosome composition and behavior. However, the mechanism of exosomes in KRAS-wild-type colorectal cancer (CRC) remains unknown. In the present study, functional analysis of overall survival post-diagnosis in patients with KRAS wild-type and those with mutant CRC was performed using human CRC specimens. Furthermore, it was demonstrated that multidrug resistance (MDR) cancer cell-derived exosomes were potentially a key factor, which promoted cetuximab-resistance in CRC cells and reduced the inhibitory effect of cetuximab in CRC xenograft models. The Cell Counting Kit-8 and colony formation assays were performed to assess the effects of exosomes derived from CRC/MDR cells on cetuximab resistance. Sphere formation assay results demonstrated that exosomes derived from CRC/MDR cells altered the self-renewal and multipotential ability of stem-cell-associated markers and facilitated resistance to cetuximab in cetuximab-sensitive cells. Furthermore, exosomes derived from CRC/MDR cells decreased sensitivity to cetuximab via the activation of PI3K/AKT signaling, which promoted Sox2 and programmed death-ligand 1 (PD-L1) mRNA and protein expression according to reverse transcription-quantitative PCR, western blotting and immunohistochemistry analyses, as well as apoptosis resistance both in vitro and in vivo according to a TUNEL assay. In conclusion, the results of the present study demonstrated that exosomes derived from CRC/MDR cells may promote cetuximab resistance in KRAS wild-type cells via activation of the PI3K/AKT signaling pathway-mediated expression of Sox2 and PD-L1, which will be useful for investigating a potential clinical target in predicting cetuximab resistance. [ABSTRACT FROM AUTHOR]

Objectives micro RNAs (mi RNAs), are non-coding RNAs that regulate gene expression, and are involved in tumour development. The aim of this study was to investigate micro RNA-497 (miR-497) expression and its role in development of colorectal cancer ( CRC). Materials and methods RT- PCR was performed to detect expression of miR-497 in CRC cell lines ( HCT8, LOVO, Ls-174, HCT116 and HT29) and in clinical cancer specimens. To further understand its role, we restored expression of miR-497 in the HCT116 cell line by transfection with miR-497 mimics or inhibitors. Effects of miR-497 on cell proliferation, migration and invasion of targets were also determined both in vitro and in vivo. Results miR-497 expression decreased in 34 CRC tissues compared to non-tumour tissues and in tumour cell lines. Overexpression of miR-497 did not inhibit cancer cell growth but suppressed metastasis and invasion both in vitro and in vivo. Vascular endothelial growth factor-A ( VEGF-A) was confirmed to be a target of miR-497. Furthermore, we found overexpression of miR-497 altered expression of key molecules of the VEGF-A/ ERK/ MMP-9 signalling pathway. Conclusions Thus our results provide evidence that miR-497 might function as a metastasis suppressor in CRC. Targeting miR-497 may provide a strategy for blocking its metastasis. [ABSTRACT FROM AUTHOR]