A plant-specific SWR1 chromatin-remodeling complex couples histone H2A.Z deposition with nucleosome sliding.

Deposition of H2A.Z in chromatin is known to be mediated by a conserved SWR1 chromatin-remodeling complex in eukaryotes. However, little is known about whether and how the SWR1 complex cooperates with other chromatin regulators. Using immunoprecipitation followed by mass spectrometry, we found all known components of the Arabidopsis thaliana SWR1 complex and additionally identified the following three classes of previously uncharacterized plant-specific SWR1 components: MBD9, a methyl-CpG-binding domain-containing protein; CHR11 and CHR17 (CHR11/17), ISWI chromatin remodelers responsible for nucleosome sliding; and TRA1a and TRA1b, accessory subunits of the conserved NuA4 histone acetyltransferase complex. MBD9 directly interacts with CHR11/17 and the SWR1 catalytic subunit PIE1, and is responsible for the association of CHR11/17 with the SWR1 complex. MBD9, TRA1a, and TRA1b function as canonical components of the SWR1 complex to mediate H2A.Z deposition. CHR11/17 are not only responsible for nucleosome sliding but also involved in H2A.Z deposition. These results indicate that the association of the SWR1 complex with CHR11/17 may facilitate the coupling of H2A.Z deposition with nucleosome sliding, thereby co-regulating gene expression, development, and flowering time.

Dual Recognition of H3K4me3 and DNA by the ISWI Component ARID5 Regulates the Floral Transition in Arabidopsis.

Chromatin remodeling and histone modifications are important for development and floral transition in plants. However, it is largely unknown whether and how these two epigenetic regulators coordinately regulate the important biological processes. Here, we identified three types of Imitation Switch (ISWI) chromatin-remodeling complexes in Arabidopsis (Arabidopsis thaliana). We found that AT-RICH INTERACTING DOMAIN5 (ARID5), a subunit of a plant-specific ISWI complex, can regulate development and floral transition. The ARID-PHD dual domain cassette of ARID5 recognizes both the H3K4me3 histone mark and AT-rich DNA. We determined the ternary complex structure of the ARID5 ARID-PHD cassette with an H3K4me3 peptide and an AT-containing DNA. The H3K4me3 peptide is combinatorially recognized by the PHD and ARID domains, while the DNA is specifically recognized by the ARID domain. Both PHD and ARID domains are necessary for the association of ARID5 with chromatin. The results suggest that the dual recognition of AT-rich DNA and H3K4me3 by the ARID5 ARID-PHD cassette may facilitate the association of the ISWI complex with specific chromatin regions to regulate development and floral transition.

Maternal vitamin D levels correlate with fetal weight and bone metabolism during pregnancy: a materno-neonatal analysis of bone metabolism parameters.

OBJECTIVES: Vitamin D plays an essential role in neonatal skeletal development and maternal weight gain during pregnancy. We aim to study the association between vitamin D status, maternal weight, and materno-neonatal bone metabolism parameters. METHODS: From January to June 2017, we conducted this cross-sectional study among 103 pregnant women (21-42 years old) and their singletons. The levels of serum 25-(OH)D, PTH, P1NP, OC, and CTX were measured for mothers and neonates (cord blood). Serum vitamin D and OC were measured using chemiluminescence and two-site immunoradiometric assay, respectively. Meanwhile, P1NP, CTX, and PTH were measured by ELISA. RESULTS: The average serum vitamin D levels from mothers were 15.1 ng/mL during pregnancy and 16.2 ng/mL in the umbilical cord. At baseline, vitamin D deficient mothers were more likely to have higher PTH (36.4 vs. 18 pg/mL; p=0.029) and lower P1NP levels (90 vs. 92.5 ng/mL; p=0.026). Also, vitamin D deficient status was associated with lower fetal weight (3,293 vs. 3,358 g; p=0.019). Maternal weight was significantly correlated with P1NP (65.86 vs. 109.35; p=0.001) and OC (14.52 vs. 18.24; p=0.038), as well as cord vitamin D level (13.31 vs. 18.46; p=0.039) among normal vs. overweight women. No significant differences were found for the correlation between maternal weight and fetal parameters except for fetal weight which significantly increased with the increase in maternal weight (overweight vs. obese women=3,280 vs. 3,560; p=0.06). CONCLUSIONS: Maternal vitamin D status is associated with maternal and neonatal bone metabolism parameters as well as maternal and neonatal weight.

The PEAT protein complexes are required for histone deacetylation and heterochromatin silencing.

In eukaryotes, heterochromatin regions are typically subjected to transcriptional silencing. DNA methylation has an important role in such silencing and has been studied extensively. However, little is known about how methylated heterochromatin regions are subjected to silencing. We conducted a genetic screen and identified an epcr (enhancer of polycomb-related) mutant that releases heterochromatin silencing in Arabidopsis thaliana We demonstrated that EPCR1 functions redundantly with its paralog EPCR2 and interacts with PWWP domain-containing proteins (PWWPs), AT-rich interaction domain-containing proteins (ARIDs), and telomere repeat binding proteins (TRBs), thus forming multiple functionally redundant protein complexes named PEAT (PWWPs-EPCRs-ARIDs-TRBs). The PEAT complexes mediate histone deacetylation and heterochromatin condensation and thereby facilitate heterochromatin silencing. In heterochromatin regions, the production of small interfering RNAs (siRNAs) and DNA methylation is repressed by the PEAT complexes. The study reveals how histone deacetylation, heterochromatin condensation, siRNA production, and DNA methylation interplay with each other and thereby maintain heterochromatin silencing.

Copper-catalyzed reactions of α,ß-unsaturated N-tosylhydrazones with diaryliodonium salts to construct N-arylpyrazoles and diaryl sulfones.

Herein, an economical copper-catalyzed reaction of α,ß-unsaturated N-tosylhydrazones with diaryliodonium salts to construct both N-arylpyrazoles and diaryl sulfones has been developed. Both the p-toluenesulfonyl anion and the 3-arylpyrazole intermediates were formed in situ from N-tosylhydrazones. Subsequently, the former reacted rapidly with diaryliodonium salts to give diaryl sulfones and aryl iodide intermediates, and the latter reacted with aryl iodide to give N-arylpyrazoles under copper-catalyzed conditions. Using unsymmetrical mesityl phenyliodonium salts as substrates, mesityl p-toluenesulfide was obtained as the major product. This reaction took full advantage of the "waste" part of substrates to form an extra diaryl sulfone.

Guaiane-type sesquiterpenoids with various ring skeletons from Daphne bholua uncovered by molecular networking and structural revisions of previously reported analogues.

The genus Daphne is a treasure-house of secondary metabolites with various biological effects, which inspired Daphne bholua being fully investigated phytochemically and biologically for the first time. Here, seven undescribed guaiane-type sesquiterpenoids (1-7) along with thirteen known analogues (8-20) were targeted and isolated from D. bholua using molecular networking. Their chemical structure and configurations were established via NMR spectroscopy analysis, NMR and ECD calculations, Snatzke's method, along with single-crystal X-ray diffraction technique. Moreover, two pairs of sesquiterpene isomers, either with prominent biological properties or with unprecedented skeleton, were revised by means of computer-assisted structure elucidation, chemical shift calculator using deep learning, etc. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico.

Salted fish and processed foods intake and nasopharyngeal carcinoma risk: a dose-response meta-analysis of observational studies.

PURPOSE: This study aims to analyze whether the consumption of salted fish and processed foods increases the risk of nasopharyngeal carcinoma by analyzing the relevant case-control or cohort design. METHODS: Major databases such as PubMed, ScienceDirect, Embase and Cochrane Library were searched to conduct related studies. In addition, Newcastle-Ottawa scale was employed for assessing the quality of articles. Random-effect model was utilized for meta-analysis. Total relative risk (RR) and 95% confidence interval (95% CI) were calculated. RESULTS: Dose response showed a consistent linear relationship between the intake of salted fish and processed foods and the risk of nasopharyngeal carcinoma. In salted fish, the summary RR was 1.23 (1.04-1.47) for low intake and 1.45 (1.19-1.76) for high intake. For processed meat, low intake was 1.33 (1.09-1.62) and high intake was 1.65 (1.35-2.02). Low intake of processed vegetables was 1.28 (1.05-1.55) and high intake was 1.45 (1.17 -1.79) for high intake. Significant heterogeneity existed in all data but decreased in some subgroups after subgroup analysis. CONCLUSION: Salted fish and processed foods are risk factors for increasing nasopharyngeal carcinoma, but they have different risk characteristics due to different intakes, different stages, and different types.

Purification of Polysaccharides from Orostachys cartilaginous Cell Cultures by Macroporous Resin Absorption and Bioactivities of the Purified Polysaccharides.

Orostachys cartilaginous is a traditional herbal medicine and its cell cultures contain large amounts of polysaccharides. To utilize the cultured O. cartilaginous cells, this study purified the crude polysaccharides of O. cartilaginous cells by macroporous resin absorption and optimized the purification process in the experiment of orthogonal design with four factors (sample concentration and volume, and eluent concentration and volume) and three levels; the antibacterial and anti-cancer effects of the purified polysaccharides (OTP) were further examined. The results showed that polysaccharide purity reached 95 % in the optimized group, i. e., 1.6 mg/mL of sample (crude polysaccharides) concentration, 3.0 bed volume (BV) of sample volume, 65 % eluent (ethanol) concentration, and 3.0 BV of eluent volume. In the antibacterial experiment, the growth of three bacterial species, i. e., Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis was inhibited by OTP, whereas that of Escherichia coli was not affected; the largest diameter of the inhibitory zone was found on B. subtilis; the extracellular alkaline phosphatase activity and the electrical conductivity, nucleic acid, and protein levels of B. subtilis increased after OTP treatment, indicating that the inhibition of B. subtilis growth was caused by the leakage of cell contents. In the anti-cancer experiment, OTP decreased the cell viabilities of the tested human cancer cells, i. e., AGS (gastric cancer), HCT116 (colon cancer), HepG2 (liver cancer), and HeLa (cervical cancer), and the highest inhibitory effect was on HCT116. OTP promoted HCT116 apoptosis and affected the expression of apoptosis-related proteins, i. e., the expression of B-cell lymphoma-2 decreased and that of bcl-2 associated X protein, cytochrome c, caspase 9 and caspase 3 increased. The findings of the present study suggest that O. cartilaginous cell cultures have a potential application in food or drug production.

MTA2 promotes the metastasis of esophageal squamous cell carcinoma via EIF4E-Twist feedback loop.

Metastasis-associated protein 2 (MTA2) is frequently amplified in many types of cancers; however, the role and underlying molecular mechanism of MTA2 in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we reported that MTA2 is highly expressed in ESCC tissue and cells, and is closely related to the malignant characteristics and poor prognosis of patients with ESCC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promoted ESCC growth, metastasis, and epithelial-mesenchymal transition (EMT) progression. This integrative analysis combined with expression microarray showed that MTA2 could interact with eukaryotic initiation factor 4E (EIF4E), which positively regulates the expression of Twist, known as a master regulator of EMT. Moreover, the results of chromatin immunoprecipitation revealed that MTA2 was recruited to the E-cadherin promoter by Twist, which reduced the acetylation level of the promoter region and thus inhibited expression of E-cadherin, and subsequently promoted the aggressive progression of ESCC. Collectively, our study provided novel evidence that MTA2 plays an aggressive role in ESCC metastasis by a novel EIF4E-Twist positive feedback loop, which may provide a potential therapeutic target for the management of ESCC.

Synthesis, Characterization of Spirocyclic λ3 -Iodanes and Their Application to Prepare 4,1-Benzoxazepine-2,5-diones and 1,3-Diynes.

Herein, a [3+2] cycloaddition of aza-oxyallylic cations with ethynylbenziodoxolones for synthesis of new λ3 -iodanes containing spirocyclic 4-oxazolidinone has been developed. This cyclic λ3 -iodanes display stability in air and excellent solubility in organic solvent. Using them as substrate, both the 4,1-benzoxazepine-2,5-diones and symmetrical 1,3-diynes derivatives were afforded in high yield under copper(I)-catalyzed conditions.

Platelet Antibodies in Infertility Patients.

BACKGROUND: Platelet antigens can stimulate the body to produce platelet alloimmune antibodies through blood transfusion, pregnancy, and autoimmunity. In the blood of pregnant women, anti-platelet antibodies can cause embryo implantation failure, abortion, etc. if they are present. METHODS: The platelet antibody was screened in 326 infertile patients (282 primary infertility and 44 secondary infertility) and 522 healthy controls in the physical examination center of our hospital by solid phase agglutination of red blood cells. RESULTS: The positive rate of anti-platelet antibody was 9.51% in the infertility group and 2.30% in the healthy control group. There was a significant difference between them (χ2 = 4.51, p < 0.05). The positive rate of anti-platelet antibody in the infertility group was significantly higher than that in the control group. The positive rate of anti-platelet antibody in the secondary infertility patients was significantly higher than that in the primary infertility patients (χ2 = 1.62, p < 0.05), and the positive rate of serum anti-platelet antibody increased gradually with the increase of infertility years. CONCLUSIONS: The positive rate of anti-platelet antibody is closely related to infertility and gradually increases with the age of infertility.

[Study on synergistic effect of Qingkailing Injection and Shengmai Injection on organ injury in endotoxemia rats].

As a dangerous disease with rapid progression, endotoxemia is easy to induce the damage to multiple organs. However, its specific and efficient treatment methods are still lacking at present. Both Qingkailing Injection(QKLI) and Shengmai Injection(SMI) have been proved effective in anti-inflammation, anti-endotoxin and organ protection. In this study, carrageenan and endotoxin were injected successively into rats to establish an endotoxemia model. Different doses of QKLI and SMI were administered to the endotoxemia rats by intraperitoneal injection separately or in combination. Then the count of white blood cells, the number of platelets, the content of cytokines, biochemical indexes, organ coefficient and pathological changes of main organs in the rats were detected. The results showed that the rats in the model group had obvious symptoms of endotoxemia, i.e., leucopenia, thrombocytopenia, increase in cytokines(IL-6 and TNF-α) and biochemical indexes of liver and kidney function as well as pathological damage to liver, kidney and lung. QKLI alone can alleviate the above symptoms of endotoxemia and the organ injury. SMI alone is less effective in improving disseminated intravascular coagulation(DIC) and cytokine secretion complicated with endotoxemia, but capable of reducing the inflammation degree of the lung, liver and kidney. The combination of QKLI and SMI remarkably increased the number of platelets in the peripheral blood, improved the liver and kidney function and reduced inflammatory factors, with lung, liver, kidney and other organ structures protected well. Moreover, the improvement effect of the combination of QKLI and SMI was stronger than those of the two injections alone at fixed doses, indicative of a synergistic effect.

miR-19 regulates the expression of interferon-induced genes and MHC class I genes in human cancer cells.

MicroRNA-19 (miR-19) is identified as the key oncogenic component of the miR-17-92 cluster. When we explored the functions of the dysregulated miR-19 in lung cancer, microarray-based data unexpectedly demonstrated that some immune and inflammatory response genes (i.e., IL32, IFI6 and IFIT1) were generally down-regulated by miR-19 overexpression in A549 cells, which prompted us to fully investigate whether the miR-19 family (i.e., miR-19a and miR-19b-1) was implicated in regulating the expression of immune and inflammatory response genes in cancer cells. In the present study, we observed that miR-19a or miR-19b-1 overexpression by miRNA mimics in the A549, HCC827 and CNE2 cells significantly downregulated the expression of interferon (IFN)-regulated genes (i.e., IRF7, IFI6, IFIT1, IFITM1, IFI27 and IFI44L). Furthermore, the ectopic miR-19a or miR-19b-1 expression in the A549, HCC827, CNE2 and HONE1 cells led to a general downward trend in the expression profile of major histocompatibility complex (MHC) class I genes (such as HLA-B, HLA-E, HLA-F or HLA-G); conversely, miR-19a or miR-19b-1 inhibition by the miRNA inhibitor upregulated the aforementioned MHC Class I gene expression, suggesting that miR-19a or miR-19b-1 negatively modulates MHC Class I gene expression. The miR-19a or miR-19b-1 mimics reduced the expression of interleukin (IL)-related genes (i.e., IL1B, IL11RA and IL6) in the A549, HCC827, CNE2 or HONE1 cells. The ectopic expression of miR-19a or miR-19b-1 downregulated IL32 expression in the A549 and HCC827 cells and upregulated IL32 expression in CNE2 and HONE1 cells. In addition, enforced miR-19a or miR-19b-1 expression suppressed IL-6 production by lung cancer and nasopharyngeal carcinoma (NPC) cells. Taken together, these findings demonstrate, for the first time, that miR-19 can modulate the expression of IFN-induced genes and MHC class I genes in human cancer cells, suggesting a novel role of miR-19 in linking inflammation and cancer, which remains to be fully characterized.

FHA2 is a plant-specific ISWI subunit responsible for stamen development and plant fertility.

Imitation Switch (ISWI) chromatin remodelers are known to function in diverse multi-subunit complexes in yeast and animals. However, the constitution and function of ISWI complexes in Arabidopsis thaliana remain unclear. In this study, we identified forkhead-associated domain 2 (FHA2) as a plant-specific subunit of an ISWI chromatin-remodeling complex in Arabidopsis. By in vivo and in vitro analyses, we demonstrated that FHA2 directly binds to RLT1 and RLT2, two redundant subunits of the ISWI complex in Arabidopsis. The stamen filament is shorter in the fha2 and rlt1/2 mutants than in the wild type, whereas their pistil lengths are comparable. The shorter filament, which is due to reduced cell size, results in insufficient pollination and reduced fertility. The rlt1/2 mutant shows an early-flowering phenotype, whereas the phenotype is not shared by the fha2 mutant. Consistent with the functional specificity of FHA2, our RNA-seq analysis indicated that the fha2 mutant affects a subset of RLT1/2-regulated genes that does not include genes involved in the regulation of flowering time. This study demonstrates that FHA2 functions as a previously uncharacterized subunit of the Arabidopsis ISWI complex and is exclusively involved in regulating stamen development and plant fertility.

miR-26a promotes hepatocellular carcinoma invasion and metastasis by inhibiting PTEN and inhibits cell growth by repressing EZH2.

A previous study revealed that therapeutic miR-26a delivery suppresses tumorigenesis in a murine liver cancer model, whereas we found that forced miR-26a expression increased hepatocellular carcinoma (HCC) cell migration and invasion, which prompted us to characterize the causes and mechanisms underlying enhanced invasion due to ectopic miR-26a expression. Gain-of-function and loss-of-function experiments demonstrated that miR-26a promoted migration and invasion of BEL-7402 and HepG2 cells in vitro and positively modulated matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, and MMP-10 expression. In addition, exogenous miR-26a expression significantly enhanced the metastatic ability of HepG2 cells in vivo. miR-26a negatively regulated in vitro proliferation of HCC cells, and miR-26a overexpression suppressed HepG2 cell tumor growth in nude mice. Further studies revealed that miR-26a inhibited cell growth by repressing the methyltransferase EZH2 and promoted cell migration and invasion by inhibiting the phosphatase PTEN. Furthermore, PTEN expression negatively correlated with miR-26a expression in HCC specimens from patients with and without metastasis. Thus, our findings suggest for the first time that miR-26a promotes invasion/metastasis by inhibiting PTEN and inhibits cell proliferation by repressing EZH2 in HCC. More importantly, our data also suggest caution if miR-26a is used as a target for cancer therapy in the future.

Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor family, induces apoptosis in a variety of cancer cells. However, gastric cancer (GC) cells are insensitive to TRAIL usually. In the previous study, we showed that Periplocin could induce apoptosis in GC cells via the activation of ERK1/2-EGR1 pathway. In the present study, we have shown that the combination of Periplocin and TRAIL had a greater inhibitory effect on gastric cancer cell viability in vitro and in vivo than Periplocin or TRAIL alone. Through upregulating the expression of DR4 and DR5 at transcriptional and protein levels, Periplocin enhanced the sensitivity of gastric cancer cells to TRAIL. Furthermore, enhanced activity of ERK1/2-EGR1 pathway was responsible for upregulating of DR4 and DR5 uponPeriplocin treatment, subsequently reducing the expression of Mcl-1 and Bcl2 and activating Bid and caspase-3/8. Collectively, these data implied that Periplocin might act as a sensitizer of TRAIL and could be a potential strategy for the treatment of GC.

A base-promoted cascade reaction of α,ß-unsaturated N-tosylhydrazones with o-hydroxybenzyl alcohols: highly regioselective synthesis of N-sec-alkylpyrazoles.

An efficient method for the synthesis of N-sec-alkylpyrazoles through a base-promoted cascade cyclization/Michael addition reaction of α,ß-unsaturated N-tosylhydrazones with ortho-hydroxybenzyl alcohols has been developed. The desired products containing di- or triaryl groups at the same carbon atom were afforded in good to excellent yields with excellent regioselectivities (>20 : 1). Moreover, a three-component reaction of ortho-hydroxybenzyl alcohols, α,ß-unsaturated N-tosylhydrazones and saturated N-tosylhydrazones also took place to afford pyrazoles in good yields. This reaction offers a new route to triarylmethanes with a simple operation and is applicable for large-scale synthesis.

Combined application of pharamcokinetic DCE-MRI and IVIM-DWI could improve detection efficiency in early diagnosis of ductal carcinoma in situ.

PURPOSE: Ductal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the early diagnosis of DCIS. METHODS: Forty-seven patients, including 25 with DCIS (age: 28-70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25-67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE-MRI and IVIM-DWI in this study. The quantitative parameters Ktrans , Kep , Ve , Vp , and D, f, D* were obtained by processing of DCE-MRI and IVIM-DWI images with Omni-Kinetics and MITK-Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares. RESULTS: All low-grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle-grade and high-grade DCIS lesions showed non-mass-like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of Ktrans , Kep , and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of Ktrans , Kep , D and the combined indicator of Ktrans , Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016). CONCLUSION: DCE-MRI and IVIM-DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over-treatment of benign lesions.

The Involvement of the RhoA/ROCK Signaling Pathway in Hypersensitivity Reactions Induced by Paclitaxel Injection.

A high incidence of hypersensitivity reactions (HSRs) largely limits the use of paclitaxel injection. Currently, these reactions are considered to be mediated by histamine release and complement activation. However, the evidence is insufficient and the molecular mechanism involved in paclitaxel injection-induced HSRs is still incompletely understood. In this study, a mice model mimicking vascular hyperpermeability was applied. The vascular leakage induced merely by excipients (polyoxyl 35 castor oil) was equivalent to the reactions evoked by paclitaxel injection under the same conditions. Treatment with paclitaxel injection could cause rapid histamine release. The vascular exudation was dramatically inhibited by pretreatment with a histamine antagonist. No significant change in paclitaxel injection-induced HSRs was observed in complement-deficient and complement-depleted mice. The RhoA/ROCK signaling pathway was activated by paclitaxel injection. Moreover, the ROCK inhibitor showed a protective effect on vascular leakage in the ears and on inflammation in the lungs. In conclusion, this study provided a suitable mice model for investigating the HSRs characterized by vascular hyperpermeability and confirmed the main sensitization of excipients in paclitaxel injection. Histamine release and RhoA/ROCK pathway activation, rather than complement activation, played an important role in paclitaxel injection-induced HSRs. Furthermore, the ROCK inhibitor may provide a potential preventive approach for paclitaxel injection side effects.

C/D-Box Snord105b Promotes Tumorigenesis in Gastric Cancer via ALDOA/C-Myc Pathway.

BACKGROUND/AIMS: Small nucleolar RNAs (snoRNAs) play an important role in carcinogenesis. In this study, we identified a C/D box snoRNA, snord105b, and further investigated the function and mechanism of the snord105b in gastric cancer (GC). METHODS: The expression level of snord105b in GC tissures, sera and cell lines were detected by qRT-PCR. Cell viability was assessed using MTS assay. Transwell and wound healing assay were performed to evaluate migration and invasion, and protein expression was examined by western blotting. ChIRP and MS analysis was used to seek for the special binding protein of snord105b. RESULTS: The snord105b was upregulated and associated with tumor size, differentiation, and pathological stage in GC. Snord105b affected proliferation, migration and invasion in multiple GC cell lines. The oncoqenic activity of snord105b was also confirmed with in vivo data. Mechanistically, snord105b specifically bound to ALDOA and affected C-myc, which plays a key role in carcinogenesis and tumor development. CONCLUSION: Snord105b appears to be a novel oncogene and is clinically and functionally involved in the development of GC. Targeting snord105b and its pathway may provide new biomarkers or potential treatments for patients with GC.