Kinesin Family Member C1 Overexpression Exerts Tumor-Promoting Properties in Head and Neck Squamous Cell Carcinoma via the Rac1/Wnt/ß-catenin Pathway.

Kinesin family member C1 (KIFC1) is a kinesin-14 motor protein, and its abnormal upregulation promotes the malignant behavior of cancer cells. N6-methyladenosine (m6A) RNA methylation is a common modification of eukaryotic messenger RNA and affects RNA expression. In this study, we explored how KIFC1 regulated head and neck squamous cell carcinoma (HNSCC) tumorigenesis and how m6A modification affected KIFC1 expression. A bioinformatics analysis was performed to screen for genes of interest, and in vitro and in vivo studies were carried out to investigate the function and mechanism of KIFC1 in HNSCC tissues. We observed that the expression of KIFC1 in HNSCC tissues was significantly higher than that in normal or adjacent normal tissues. Patients with cancer with higher KIFC1 expression have a lower tumor differentiation status. Demethylase alkB homolog 5, a cancer-promoting factor in HNSCC tissues, could interact with KIFC1 messenger RNA and posttranscriptionally activate KIFC1 through m6A modification. KIFC1 downregulation suppressed HNSCC cell growth and metastasis in vivo and in vitro. However, overexpression of KIFC1 promoted these malignant behaviors. We demonstrated that KIFC1 overexpression activated the oncogenic Wnt/ß-catenin pathway. KIFC1 interacted with the small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1) at the protein level and increased its activity. The Rho GTPase Rac1 was indicated to be an upstream activator of the Wnt/ß-catenin signaling pathway, and its Rac1 inhibitor, NSC-23766, treatment reversed the effects caused by KIFC1 overexpression. Those observations demonstrate that abnormal expression of KIFC1 may be regulated by demethylase alkB homolog 5 in an m6A-dependent manner and promote HNSCC progression via the Rac1/Wnt/ß-catenin pathway.

Expression of neutrophil adhesion molecule CD11b as an early diagnostic marker for neonatal sepsis / 中华儿科杂志

<p><b>OBJECTIVE</b>Neonatal sepsis is a common disease and the sepsis-related mortality rate is still high. Until now, there has no ideal diagnostic marker to early identify neonatal sepsis. Expression of neutrophil adhesion molecule CD(11b) was showed as the earlier reaction to the infection/inflammation, and may be applied as an early diagnostic marker for sepsis. This study was to investigate this antigen for early diagnosis of neonatal sepsis related to bacterial infection.</p><p><b>METHODS</b>According to clinical symptoms, signs and four indices (WBC, PLT, plasma CRP and ratio of I/T), fifty-one neonates with established or suspected sepsis were allocated retrospectively into two groups of sepsis [n = 23, gestational age of (38.3 +/- 2.4) weeks, postnatal age of (12.7 +/- 8.8) days, body weight: (3.1 +/- 0.8) kg] and suspected sepsis [n = 28, gestational age of (38.8 +/- 1.6) weeks, postnatal age of (11.7 +/- 7.3) days, body weight: (3.3 +/- 0.6) kg]. Fifteen healthy neonates were served as controls [gestational age: (38.5 +/- 1.4) weeks, postnatal age: (8.2 +/- 5.5) days, body weight: (3.3 +/- 0.3) kg]. CD(11b) was quantified with the whole blood flow cytometry and direct immunofluorescence technique.</p><p><b>RESULTS</b>The expressions of neutrophil CD(11b) in neonates with sepsis and suspected sepsis were (320 +/- 189) MFI and (456 +/- 213) MFI, respectively, which was lower than that of controls [(1,090 +/- 338) MFI, t = -9.01 and -7.56, respectively; P < 0.001]. The expression of CD(11b) was lower in neonates with sepsis than that with suspected sepsis (t = -2.39, P < 0.05). The expression of CD(11b) in neonates with CRP >or= 30 mg/L was (211 +/- 164) MFI, which was lower than those with CRP < 30 mg/L [(505 +/- 265) MFI, t = 2.64, P < 0.05]. The detection of CD(11b) (<or= 600 MFI) for suspected sepsis showed a sensitivity of 86.3%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 68.2%. The positive rate of CD(11b) detection was 86.3%, which was higher than the blood culture test (17.6%, chi(m)(2) = 31.2, P < 0.05).</p><p><b>CONCLUSION</b>The expression of CD(11b) in neonatal sepsis presented with a down-regulation and, the decreased CD(11b) expression might be related to the severity of infections. For the neonatal sepsis the serial measurements of neutrophil CD(11b) expression with the whole blood flow cytometry seemed feasible and reliable in the early diagnosis, evaluation of infection severity and observation of therapy reactions.</p>