ABSTRACT
Objective:To investigate the diagnostic value of circular RNA circ_100367 in thyroid cancer (THCA) and its relationship with immune-related factors.Methods:According to the data chip provided by the National Center for Biotechnology Information (NCBI) website, the differentially expressed circRNAs in THCA were analyzed, then circ_100367 was included in this study. The serum of 175 THCA patients and healthy people were collected, and the expression levels of circ_100367 and its linear transcript DCAF8 mRNA in serum samples were detected by qRT-PCR, and the correlation between circ_100367 and DCAF8 was calculated. The correlation between the expression of circ_100367 and the clinicopathological characteristicsof the patients, immune infiltration level and immunosuppressive factor PD-1 was analyzed.Results:Compared with serum of healthy people (1.00±0.37) , expression level of circ_100367 in serum of THCA patients was significantly increased (1.37±0.41) ( t=8.80, P<0.001) , and there was no significant difference in DCAF8 mRNA expression ( t=1.67, P=0.095) , but circ_100367 was positively correlated with DCAF8 mRNA expression ( r=0.17, P=0.028) . Analysis of expression and clinicopathological characteristics of circ_100367 showed that compared with patients in M0 group (1.26±0.40) , circ_100367 was overexpressed in M1 and Mx patients (1.43±0.40) ( t=2.63, P=0.009) ; compared with N0 patients (1.24±0.36) , circ_100367 was overexpressed in serum of N1 and Nx patients (1.45±0.42) ( t=3.48, P=0.001) ; compared with serum of patients with negative lymph node detection (1.28±0.36) , circ_100367 was overexpressed in serum of positive patients (1.42±0.43) ( t=2.14, P=0.034) ; compared with T1+T2 stage patients (1.30±0.37) , circ_100367 expression was overexpressed in serum ofT3+T4 patients (1.40±0.43) ( t=2.22, P=0.028) . Analysis of the expression and immune infiltration levels of circ_100367 found that highly expressed circ_100367 was associated with CD8+ T cells ( r=0.25, P=0.024) , macrophages ( r=0.22, P=0.038) , CD4+ T cells ( r=0.25, P=0.020) and B cell ( r=0.23, P=0.033) levels. The expression of circ_100367 was also positively correlated with the immunosuppressive factor PD-1 ( r=0.19, P=0.011) . Conclusion:circ_100367 can be used as a marker for the diagnosis of THCA and its expression is strongly correlated with immune-related factors.
ABSTRACT
Cullin-RING E3 ubiquitin ligase (CRL)-4 is a member of the large CRL family in eukaryotes. It plays important roles in a wide range of cellular processes, organismal development, and physiological and pathological conditions. DDB1- and CUL4-associated factor 8 (DCAF8) is a WD40 repeat-containing protein, which serves as a substrate receptor for CRL4. The physiological role of DCAF8 is unknown. In this study, we constructed Dcaf8 knockout mice. Homozygous mice were viable with no noticeable abnormalities. However, the fertility of Dcaf8-deficient male mice was markedly impaired, consistent with the high expression of DCAF8 in adult mouse testis. Sperm movement characteristics, including progressive motility, path velocity, progressive velocity, and track speed, were significantly lower in Dcaf8 knockout mice than in wild-type (WT) mice. However, the total motility was similar between WT and Dcaf8 knockout sperm. More than 40% of spermatids in Dcaf8 knockout mice showed pronounced morphological abnormalities with typical bent head malformation. The acrosome and nucleus of Dcaf8 knockout sperm looked similar to those of WT sperm. In vitro tests showed that the fertilization rate of Dcaf8 knockout mice was significantly reduced. The results demonstrated that DCAF8 plays a critical role in spermatogenesis, and DCAF8 is a key component of CRL4 function in the reproductive system.