ABSTRACT
Purpose@#Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. @*Materials and Methods@#RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. @*Results@#We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. @*Conclusion@#Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.
ABSTRACT
Objective To explore the effect of chest circumference index adjusting tube voltage techniquey on image quality and radiation dose at coronary CTA. Methods One hundred and twenty consecutive patients [body mass index(BMI)90 cm, n=20). All patients were examined by coronary CTA. The patients in conventional group were performed using retrospective ECG-gating technology and reconstructed by filtered back projection algorithm. The tube voltage/tube current was 120 kV/1 000 mAs. Prospective ECG?gating technology and iterative algorithm reconstruction were used in low dose group. The tube voltages/currents were 80 kV/150 mAs, 100 kV/150 mAs, 120 kV/150 mAs in A, B, C group, respectively. Image quality was assessed by subjective evaluation (image quality score) and objective evaluation (signal?to?noise ratio).The effective radiation dose was calculated. Analyses of the differences between groups were compared with image quality, radiation dose by single factor variance and Wilcoxon signed ranks test.Results The image quality scores and signal?to?noise ratio of aorta were respectively (3.47 ± 0.38), (3.48 ± 0.27), (3.45 ± 0.32), (3.46±0.29) and (15.5±3.6), (15.8±3.6), (15.8±4.1), (16.2±3.9) in conventional, A, B and C groups, there was no statistical difference between the four groups (P=0.24, 0.43). The effective radiation dose of four groups were respectively (17.15 ± 3.25), (0.88 ± 0.02), (1.38 ± 0.05), (2.32 ± 0.04) mSv, the difference was statistically significant (P=0.02). The effective radiation dose of A, B, C group was significantly lower than that in the conventional group. Conclusion Chest circumference index adjusting tube voltages technology at coronary CT angiography can effectively reduce the effective radiation without compromise of image quality.