Estrogen-mediated DNMT1 and DNMT3A recruitment by EZH2 silences miR-570-3p that contributes to papillary thyroid malignancy through DPP4.

BACKGROUND: Papillary thyroid carcinoma (PTC) is a common endocrine malignancy. Studies have indicated that estrogen can regulate the expression of miRNAs in numerous malignancies. MiR-570-3p has been shown to have a regulatory function in various cancers. However, studies of the regulatory function of miR-570-3p and a direct link between estrogen (especially estradiol E2) and miR-570-3p in PTC have not been done. METHODS: Expression of miR-570-3p and its downstream target DPP4 in PTC tissues and cells was predicted using bioinformatics and validated by qRT-PCR and western blot assays. We then performed a series of gain-and-loss experiments to assess the functional significance of miR-570-3p/DPP4 axis in PTC progression in vitro and in vivo. Additionally, the methylation of the miR-570-3p promoter region was examined via bioinformatics analysis and MSP. Finally, the effects of E2 on PTC progression and the correlation between DNMT1/DNMT3A and EZH2 were predicted by bioinformatic tools and proved by luciferase reporter, ChIP, and co-IP assays. RESULTS: In PTC tumor tissues and cell lines, there was a lower expression level and a higher methylation level of miR-570-3p compared to normal tissues and cell lines. DPP4 was identified as the downstream target of miR-570-3p. Overexpression of miR-570-3p reduced the proliferative, migratory, and invasive capabilities, and promoted apoptosis, while overexpression of DPP4 reversed these effects in PTC cells. It was also discovered that DNMT1 and DNMT3A increased the CpG methylation level of the miR-570-3p promoter in an EZH2-dependent manner, which led to decreased expression of miR-570-3p. Furthermore, we observed that estrogen (E2) enhanced the methylation of miR-570-3p and suppressed its expression levels, resulting in augmented tumor growth in vivo in PTC. CONCLUSION: Estrogen regulates the EZH2/DNMTs/miR-570-3p/DPP4 signaling pathway to promote PTC progression.

Research space telescope deployable mechanism variable diameter internal drive device elastic collision contact characteristics in the inter-stage transition.

To address the problem of elastic contact discrepancies between a variable-diameter internal drive device and a non-continuous surface during the transition, caused by the vibrations resulting from elastic collision impact when the motion speed of the elastic body increases, the following steps were taken. First, we established models for elastic collision, impact, and vibration during the inter-stage transition to analyze how motion speed and preload affect the elastic contact characteristics between the two components. Subsequently, we employed the finite element method to further analyze the elastic contact state, using identical loads but varying motion speeds and radial preloads as boundary conditions. Finally, an experimental prototype was developed to validate the elastic contact state of the elastic body during the inter-stage transition. The results indicated that the amplitude of elastic body vibration increased with higher motion speed, while it decreased with higher radial preload. Therefore, it is necessary to adjust radial preload at different times to ensure effective elastic contact between the elastic body and the non-continuous surface during the inter-stage transition. This approach not only enhances deployment speed but also guarantees the stability of the inter-stage transition.

PFKFB4 negatively regulated the expression of histone acetyltransferase GCN5 to mediate the tumorigenesis of thyroid cancer.

Thyroid cancer (TC) is the most common malignant endocrine tumor, and its incidence has progressively increased over several decades. Accumulating evidence has suggested that PFKFB4, a critical regulatory enzyme of glycolysis, has been implicated in various solid cancers. However, the exact effect of PFKFB4 on TC remains unclear. Hence, the objective of this work was to investigate the role of PFKFB4 in TC and explore the underlying regulatory mechanisms. Here, we provide evidence that mRNA levels of PFKFB4 were upregulated in TC patients' thyroids and cell lines. Downregulation of PFKFB4 reduced TC cell viability and inhibited colony formation. In addition, the migration and invasion of TC cells were suppressed by PFKFB4 knockdown, suggesting that PFKFB4 is positively correlated with tumorigenesis of TC. Molecularly, knockdown of PFKFB4 significantly inhibited expression of GCN5 and phosphorylation of PI3K/AKT. Moreover, the suppressive role of shPFKFB4 in TC cell growth was reversed by upregulation of GCN5. Finally, the in vivo experiment indicated that downregulation of PFKF4B suppressed tumor growth in xenografts TC model mice. In total, our results suggested that PFKFB4-mediated TC tumorigenesis by positively regulating GCN5 and PI3K/AKT signaling. These findings provide new research directions and therapeutic options considering PFKF4B as a novel diagnosis marker and therapeutic target.

[Preoperative evaluation of multi-slice spiral computed tomography angiography in laparoscopic radical operation for colorectal carcinoma].

OBJECTIVE: To investigate the clinical application of 256 multi-slice spiral computed tomography angiography (MSCTA) technique in the preoperative evaluation of mesenteric angiography in order to provide a reference to vessel anatomy and dissociation in laparoscopic radical operation for colorectal carcinoma. METHODS: Clinical data of 50 patients with colorectal cancer who underwent preoperative MSCTA+FDCT and laparoscopic curative operation at our hospital from October 2013 to March 2015 were collected (MSCTA group). The evaluation item was visualization of mesenteric artery, which was compared with the findings under laparoscopic surgery. Meanwhile, another 50 colorectal cancer patients undergoing laparoscopic radical operation by the same surgeon team without preoperative MSCTA examination were used as control(control group). Clinical data were compared between the two groups. RESULTS: MSCTA precisely and correctly demonstrated anatomy and variations of the mesenteric artery and relative nutrient vessel in carcinoma. The angiography reconstruction images were consistent with the visual anatomy and variation from laparoscopic findings, whose diagnostic conformity rate of 100%. As compared to control group, operative time was shorter [(195.0±23.2) minutes vs.(218.0±19.6) minutes, t=8.326, P=0.015], and blood loss was less[(168.1±18.8) ml vs. (206.5±14.3) ml, t=-19.369, P=0.002] in MSCTA group. Differences of number of harvested lymph node, postoperative complication morbidity, postoperative hospital stay and hospitalization cost were not significant between two groups(all P>0.05). CONCLUSION: Preoperative MSCTA can demonstrate anatomy and variations of the mesenteric artery precisely and correctly, thus it is beneficial to shorten the operation time and to reduce blood loss.