Long noncoding RNAs (LncRNAs), including MALAT1, are critical regulators of tumor development. However, the roles and molecular mechanisms of LncRNAs in cutaneous squamous cell carcinoma (cSCC) remain underexplored. In this study, functional studies using in vitro cellular and in vivo xenograft models confirmed the pro-carcinogenic roles of MALAT1 in cSCC. Further, MALAT1 was identified to regulate epidermal growth factor receptor (EGFR) protein expression but did not affect EGFR mRNA expression. Transcriptomic sequencing identified kinectin 1 (KTN1) as the key mediator for MALAT1 regulation of EGFR. Mechanistic study revealed that MALAT1 interacts with c-MYC to form a complex and directly binds to the promoter region of KTN1 gene and enhances its transactivation to positively regulate EGFR protein expression. Our findings, therefore, establish a novel c-MYC-assisted MALAT1-KTN1-EGFR axis, which contributes to cSCC development and may serve as novel target for therapeutic intervention.

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The development of cutaneous squamous cell carcinoma (cSCC) is associated with activation of the epidermal growth factor receptor (EGFR). EGFR-targeting presents a promising strategy for improving therapeutic efficacy. However, recent studies have suggested that tumours overexpressing EGFR depend on autophagy for survival and exhibit resistance to EGFR-targeting drugs. Chloroquine diphosphate (CQ), an autophagy inhibitor that may enhance the cytocidal effect of gefitinib against cSCC, was used in the present study. Cytotoxicity assays were performed to determine the half-maximal inhibitory concentration values of gefitinib and CQ in A431 cells. Drug interaction was analysed using CompuSyn software, which also determined combination index and dose reduction index values. Apoptosis and autophagy of A431 cells were investigated via flow cytometry, western blotting analyses, acridine orange/ethidium bromide staining and monodansylcadaverine staining. Suppression of autophagy by CQ, which was demonstrated by an alteration in microtubule associated protein 1 light chain 3-B in CQ pre-treated A431 cells, significantly enhanced cell apoptosis, which suggested that gefitinib-induced autophagy is cytoprotective. Thus, CQ was demonstrated to exhibit a synergistic apoptotic effect when used in combination with gefitinib during cSCC therapy. Further in vivo investigations are required to confirm the results of the present study.

The present review evaluated the effect of hyperbaric oxygenation (HBO) therapy on post-concussion syndrome (PCS). Searches for publications from the earliest date possible up until the first week of 2016 were conducted using the electronic databases Cochrane, EBSCOhost, Embase, Ovid MEDLINE, PubMed and Web of Science. Additional trials were identified through reference list scanning. Randomized controlled trials assessing the effectiveness of HBO therapy in PCS were selected and tested for eligibility for inclusion in the present review. Two independent reviewers conducted data extraction and the Cochrane Collaboration's recommended method was used to assess the risk of bias in each study included. Review Manager 5.3 software was used for data synthesis and analysis and the standardized mean difference (SMD) or mean difference (MD) was estimated with a fixed or random effects model using a 95% confidence interval (CI). A total of 127 articles were identified, 4 of which were eligible for final analysis. The meta-analysis identified no difference in the Rivermead Post-Concussion Symptoms Questionnaire (MD=1.23; 95% CI, −3.47-5.94; P>0.05; I2=35%) or Post-Traumatic Stress Disorder Checklist (PCL) scores (SMD=0.12; 95% CI, −0.31-0.54; P>0.05; I2=0%) scores between groups receiving different oxygen doses. The differences in PCL scores (SMD=−0.13, 95% CI, −0.80-0.53; P>0.05; I2=63%) and neurobehavioral symptoms (SMD=−1.00, 95% CI, −2.58-0.58; P>0.05; I2=92%) between the HBO and sham groups were not significant. The current study demonstrated that HBO therapy has no significant effect on PCS compared with the sham group. Therefore, it was determined that effective design and execution of a large clinical trial, which includes treatment, control and sham groups is required in the future.

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