Background: MicroRNAs (miRNAs), the key regulator of gene expression, and N6‐methyladenosine (m6A) RNA modification play a significant role in tumour progression. However, regulation of m6A‐modified mRNAs by miRNAs in colorectal cancer (CRC), and its effect on progression of CRC, remains to be investigated.Methods: Expression of miR‐6125 and YTH Domain‐Containing Family Protein 2 (YTHDF2) was detected by western blotting and immunohistochemistry. The effects of miR‐6125 and YTHDF2 on proliferative capacity of CRC cells were analysed using soft agar, ATP, CCK8 and EdU assays, and in animal experiments.Results: MiR‐6125 expression was downregulated markedly in CRC, and expression correlated negatively with tumour size and prognosis. MiR‐6125 targeted the 3′‐UTR of YTHDF2 and downregulated the YTHDF2 protein, thereby increasing the stability of m6A‐modified glycogen synthase kinase 3 beta (GSK3β) mRNA. Increased GSK3β protein levels inhibited the expression of Wnt/β‐catenin/Cyclin D1 pathway‐related proteins, leading to G0‐G1 phase arrest and ultimately inhibiting the proliferation of CRC cells.Conclusions: MiR‐6125 regulates YTHDF2 and thus plays a critical role in regulating the Wnt/β‐catenin pathway, thereby affecting the growth of CRC. Collectively, these results suggest that miR‐6125 and YTHDF2 are potential targets for treatment of CRC.

Although several previous studies have reported the implication of various microRNAs (miRNAs) in regulation of human bladder cancer (BC) development, alterations and function of many miRNAs in bladder cancer growth are not explored yet at present. Here, we screened 1,900 known miRNAs and first discovered that miR-411 was one of the major miRNAs, which was down-regulated in n-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced BCs. This miR-411 down-regulation was also observed in human BC tissues and cell lines. The results from evaluating the relationship between miR-411 and patient survival in BC using the TCGA (The Cancer Genome Atlas) database indicated that miR-411 was positively correlated with DFS (disease-free survival). Our studies also showed that miR-411 inhibited tumor growth of human BC cells in a xenograft animal model. Mechanistic studies revealed that overexpression of miR-411 repressed the expression of ALL1-fused gene from the chromosome 1q (AF1q) (MLLT11) by binding to the 3' untranslated region (UTR) of mllt11 mRNA and in turn induced p21 expression and caused cell cycle arrest at the G2/M phase, further inhibiting BC tumor growth. Collectively, our results improve our understanding of the role of miR-411 in BC tumor growth and suggest miR-411 and MLLT11 as potential new targets for the treatment of BC patients.

Background: Lung cancer is the leading cause of cancer-related death worldwide and it is critical to discover specific biomarkers to provide better individualized treatment and subsequently better prognosis. The sirtuins (SIRT1–7) have been reported to be involved in cancers including non-small cell lung cancer (NCSLC), however, the results are not consistent and not all the seven sirtuins are explored and compared. Methods: TCGA data was downloaded and used to investigate and compare the associations of sirtuins mRNA levels with clinicopathological parameters and prognosis in NSCLC. Results: Our results suggested SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adenocarcinoma (ADC) patients and female patients while SIRT5 were highly expressed in squamous cell carcinoma (SCC) patients and male patients. Associations of high SIRT7 with younger onset age, high SIRT1 with distant metastasis and low T stage, and high SIRT4 with high T stage and TNM stage were also found. Kaplan-Meier plot curves and univariate Cox proportional regression analyses indicated that high SIRT2, SIRT4, and SIRT6 expressions were associated with longer overall survival (OS) time. Multivariate analyses indicated that SIRT2 and SIRT6 were still associated with OS. For recurrence-free survival (RFS), high SIRT1 expression was significantly associated with shorter RFS time while high SIRT2-3 and SIRT5-7 expressions were associated with longer RFS time in univariate analyses. After adjusting the confounding factors, significant associations were still found in SIRT1-2 and SIRT5-7 but not in SIRT3. We also stratified the patients by combining SIRT1 and SIRT2 and revealed that the combination of SIRT1 and SIRT2 was a better prediction model for RFS in NSCLC. To preliminarily understand the potential mechanisms of sirtuins in NSCLC carcinogenesis, the genes co-expressed with sirtuins were analyzed and annotated. Conclusion: sirtuins might be the potential therapy targets and prognostic biomarkers in NSCLC.

Objective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection. Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System. Results: Our results showed that serum IL-6, IL-8, TNF-α, IL-1β, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p< 0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (all p< 0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p< 0.05). Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.

Background: Metastasis is the leading cause of death in patients with bladder cancer (BC). However, current available treatments exert little effects on metastatic BC. Moreover, traditional grading and staging have only a limited ability to identify metastatic BC. Accumulating evidence indicates that the aberrant expression of microRNA is intimately associated with tumor progression. So far, many miRNAs have been identified as molecular targets for cancer diagnosis and therapy. This study focused on the role of miR‐516a‐5p (miR‐516a) in BC.Methods: MiR‐516a expression and its downstream signaling pathway were detected using molecular cell biology and biochemistry approaches and techniques. Fresh clinical BC tissue was used to study the clinicopathological characteristics of patients with different miR‐516a expression. The biological functions of miR‐516a in BC were tested both in vivo and in vitro.Results: A more invasive BC phenotype was significantly and positively correlated with miR‐516a overexpression in BC patients. MiR‐516a inhibition significantly decreased BC cell invasion and migration in vitro and in vivo. Furthermore, miR‐516a attenuated the expression of PH domain leucine‐rich repeat‐containing protein phosphatase 2 protein and inhibited SMAD‐specific E3 ubiquitin protein ligase 1 transcription by activating the AKT/Forkhead box O3 signaling pathway, which stabilized MMP9 and slowed down its proteasomal degradation, ultimately promoting BC motility and invasiveness.Conclusions: Our findings reveal the crucial function of miR‐516a in promoting BC metastasis, and elucidate the molecular mechanism involved, suggesting that miR‐516a may be a promising novel diagnostic and therapeutic target for BC.