MicroRNAs (miRNAs) play an important role in carcinogenesis and cancer progression. The purpose of this study was to identify miRNAs associated with carcinoma function in OSCC and to investigate the potential role of the specific miRNAs. First, a comprehensive microarray analysis was performed, and miR-142-5p was identified as a candidate miRNA involved in OSCC. miR-142-5p has been reported to show high expression levels in cancer patients and to be involved in tumor growth and metastasis. However, the expression and function of miR-142-5p in oral squamous cell carcinoma (OSCC) are not fully characterized. We evaluated miR-142-5p expression in both OSCC-derived cell lines and primary OSCC tissues and performed functional analysis of miR-142-5p in OSCC-derived cell lines using mimics and inhibitors. miR-142-5p expression was up-regulated in OSCC tissues and OSCC cell lines. Overexpression of miR-142-5p significantly promoted the proliferation and invasion of OSCC cells. Bioinformatics analysis was performed using TargetScan to predict potential target sites that match the seed region of miR-142-5p. Phosphatase and tensin homolog deleted on chromo-some 10 (PTEN) was identified as a potential target and selected for further analysis. PTEN expression levels were down-regulated and AKT expression levels were up-regulated in miR-142-5p-overexpressing cells. We have shown that miR-142-5p targets the PTEN gene and is involved in cancer progression. Our results suggest that miR-142-5p is involved in the progression of OSCC by controlling the phosphatidylinositol 3-kinase (PI3K)/AKT pathway by targeting the PTEN gene. Our findings suggest that miR-142-5p may be a new target for the treatment of OSCC.

Oxidative stress (OS) contributes to nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. We investigated whether antioxidative self-assembling nanoparticles (SMAPo^TN) could reduce the development of NASH and hepatocellular carcinoma (HCC) in p62/Sqstm1 and Nrf2 double knockout (DKO) mice and studied protective mechanisms. We measured disease development in male DKO mice fed a normal chow (NASH model) or a 60% high-fat diet (HFD; HCC model) with or without SMAPo^TN administration for 26 weeks. SMAPo^TN inhibited liver fibrosis in both groups and prevented HCC development (0% vs. 33%, p < 0.05) in the HFD group. SMAPo^TN reduced OS, inflammatory cytokine signaling, and liver fibrosis. RNA-sequencing revealed that SMAPo^TN decreased endoplasmic reticulum stress signaling genes in both groups, HCC driver genes, and cancer pathway genes, especially PI3K-AKT in the HFD groups. In the SMAPo^TN treatment HFD group, serum lipopolysaccharide levels and liver lipopolysaccharide-binding protein expression were significantly lower compared with those in the nontreatment group. SMAPo^TN improved the α-diversity of gut microbiota, and changed the microbiota composition. Oral SMAPo^TN administration attenuated NASH development and suppressed hepatocarcinogenesis in DKO mice by improving endoplasmic reticulum stress in the liver and intestinal microbiota. SMAPo^TN may be a new therapeutic option for NASH subjects and those with a high HCC risk.

Elective neck dissection (END) is recommended for the management of patients with oral squamous cell carcinoma (OSCC) because of the risk of occult metastasis (OM). We hypothesized that some factors predict poor prognosis regardless of a cN0 END. This study aimed to investigate the predictors of OM and prognostic factors in patients with cN0 OSCC who underwent supraomohyoid neck dissection (SOHND). A retrospective cohort study design was created and implemented. The primary predictive variables in this study were OM and risk factors for poor prognosis after SOHND. A Cox proportional hazard model was used to adjust for the effects of potential confounders on the risk factors for poor prognoses. Among 86 patients with OSCC, OMs were observed in 9 (10.5%). The neutrophil-to-lymphocyte ratio (NLR) and vascular invasion are good markers for detecting OM. A Cox multivariable analysis identified two independent predictors of overall survival: pathologic node (pN) and laterality of END. An independent predictive factor for disease-free survival, the surgical margin, was also identified in this study. According to the pN classification, pN1 patients had a worse survival rate than pN2 patients. Therefore, in the case of pN1, regardless of being cN0, additional adjuvant therapy may be necessary.

Introduction In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC. Methods and analysis This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias. Ethics and dissemination This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals. Trial registration number UMIN000027875.