Background Functions of CircMET (hsa_circ_0082002) which is a circular RNA and derived from MET gene remain understood incompletely. In the present study, Xp11.2 translocation/NONO-TFE3 fusion renal cell carcinoma (NONO-TFE3 tRCC) with up-regulated CircMET was employed to investigate its mechanism in cancer progression and post-transcriptional regulation. Methods FISH and real-time PCR were performed to explore the expression and localization circMET in NONO-TFE3 tRCC tissues and cells. The functions of circMET in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay. The regulatory mechanisms among circMET, CDKN2A and SMAD3 were investigated by luciferase assay, RNA immunoprecipitation, RNA pulldown and targeted RNA demethylation system. Results The expression of circMET was upregulated by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells, and overexpression of circMET significantly promoted the growth of NONO-TFE3 tRCC. Mechanistic studies revealed that circMET was delivered to cytosol by YTHDC1 in N6-methyladenosine (m6A)-depend manner. CircMET enhances mRNA decay of CDKN2A by direct interaction and recruitment of YTHDF2. Meanwhile, circMET competitively absorbed miR-1197 and prevented those from SMAD3 mRNA. Conclusions CircMET promotes the development of NONO-TFE3 tRCC, and the regulation to both CDKN2A and SMAD3 of circMET was revealed. CircMET has the potential to serve as a novel target for the molecular therapy of NONO-TFE3 tRCC as well as the other cancer with high-expressing circMET.

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This study aimed to compare the clinicopathologic features and prognosis in patients with Xp11 translocation renal cell carcinomas (RCCs). In total, 8083 RCCs were screened at five centres from January 2007 to December 2018, including 8001 adults (≥18 years) and 82 children (<18 years). Finally, 73 adults and 17 children were identified as Xp11 translocation RCCs, accounting for 1.1% (90 of 8083) of the RCCs. However, 4 children and 1 adult were excluded because of loss to follow-up when performing the survival analysis. The proportion of paediatric and adult Xp11 translocation RCCs was 20.7% (17 of 82) and 0.9% (73 of 8001) of RCCs, respectively, and the incidence in children and adults was significantly different (P < 0.01). Lymph node positivity (LN+) most commonly occurred in children (58.8%) compared with adults (28.8%; P = 0.02), but children with LN+ showed significantly higher fiveyear overall survival and progression-free rates (OS: 75.0%; PFS: 64.8%) than adult patients (OS: 40.3%; PFS: 0%) (log-rank P pfS < 0.01; P oS = 0.04). Multivariable analysis indicated that local lymph node metastasis was associated with both PFS (HR = 0.10; 95% CI 0.02-0.51; P = 0.01) and OS (HR = 0.11; 95% CI 0.01-0.98; P = 0.04) in adults. Adult patients with LN+ may indicate a worse prognosis than paediatric patients.Xp11 translocation renal cell carcinomas (RCCs) are characterized by several different chromosomal translocations involving Xp11 and the formation of TFE3 fusion genes, followed by overexpression of TFE3 protein 1 . The first case was a 2.4-year-old child diagnosed by karyotype analysis in 1986 2 . In 2004, Xp11 translocation RCCs were classified as a distinct entity of RCC by the World Health Organization (WHO) 3 . Recent reports have found that RCC associated with t(6; 11) (p2l; q12)/TFEB gene fusions is exceedingly similar to Xp11 translocation RCCs with respect to clinical characteristics, pathology, and molecular genetics 4 . Given that both TFE3 and TFEB pertain to the microphthalmia-associated transcription factor family, Xp11 translocation RCCs and RCC associated 1

The research was performed to explore the diagnosis value of dynamic serum calprotectin (SC) expression for sepsis in postoperative intensive care unit patients. One hundred sixty-three patients who met the inclusion criteria served as the study group. All cases in the study group were further divided into the sepsis subgroup (51 cases) and the nonsepsis subgroup (112 cases). Fifty healthy volunteers served as the control group. The levels of SC and other laboratory indexes including complete blood counts, leukocytes, the immature-to-total-neutrophil ratio, procalcitonin (PCT), C-reactive protein, and blood lactate were detected, cytokines [interleukin (IL)-2, IL-6, and interferon-γ] released by neutrophils were also determined. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the Sequential Organ Failure Assessment score were calculated. The factors related to prognosis were analyzed with multivariate logistic regression analysis. The diagnostic accuracies of ΔSC [the differences of SC levels between postoperative day (POD) 1 and POD 2, 3, 5, 7] and ΔPCT (the differences of PCT levels between POD 1 and POD 2, 3, 5, 7) on sepsis were compared with other markers for sepsis. The levels of SC and cytokines were markedly increased on POD 1, 2, 3, 5, and 7 in the study group compared with the control group (P < 0.05 or P < 0.01). The same results were found in the sepsis subgroup compared with the nonsepsis subgroup (P < 0.05 or P < 0.01). Significant positive correlations between SC and cytokines were confirmed in patients of the study group (P < 0.05 or P < 0.01). APACHE II scores and the levels of SC and PCT on POD 1 were the variables significantly associated with sepsis. The diagnostic accuracies of ΔSC (sensitivity 87%, specificity 89%) and ΔPCT (sensitivity 89%, specificity 90%) for sepsis were greater than other ΔSCs and ΔPCTs. It appears that the dynamic changes in SC are of the predictive values for septic patients after major surgeries.