Long non-coding RNA PVT1 facilitates cell migration and invasion by regulating miR-148a-3p and ROCK1 in breast cancer.

PURPOSE: Breast cancer (BC) is one of the most common malignant tumors for women. The role and potential mechanisms of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) were explored in BC cell migration and invasion. METHODS: PVT1, miR-148a-3p and Rho­associated, coiled­coil containing protein kinase 1 (ROCK1) mRNA expressions were detected using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The ROCK1 protein expression was detected by Western blotting. The relationship of PVT1, miR-148a-3p and ROCK1 was analyzed by Dual Luciferase activity, RNA immunoprecipitation (RIP) and Spearman correlation analysis. Cell invasion and migration were detected by Transwell assay. RESULTS: Upregulation of PVT1 and ROCK1, and downregulation of miR-148a-3p were observed in BC tissues and cell lines. According to the analysis of Dual Luciferase activity, RIP and Spearman correlation analysis, miR-148a-3p directly binds to PVT1, and ROCK1 is a target of miR-148a-3p. In addition, PVT1 regulated the cells migration and invasion by regulating miR-148a-3p and ROCK1 expression. CONCLUSION: These data demonstrated that PVT1 was upregulated and facilitated to the cell migration and invasion of BC by the regulation of miR-148a-3p and ROCK1, indicating that PVT1 may be a potential biomarker of BC diagnosis and treatment.

MicroRNA-141-3p promoted the progression of nasopharyngeal carcinoma through targeting DLC1.

OBJECTIVE: Previous studies have shown that the function of miR-141 has tissue specificity. However, the role of miR-141-3p has not been reported in nasopharyngeal carcinoma (NPC). Therefore, this study explored the function of miR-141-3p in NPC. PATIENTS AND METHODS: MiR-141-3p expression in NPC tissues was examined via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Cell Counting Kit-8 (CCK-8) and transwell assays were used to explore the function of miR-141-3p. The relationship between miR-141-3p and DLC1 was verified by Dual-Luciferase assay. Protein expression was observed by immunocytochemical assay and Western blot analysis. RESULTS: Upregulation of miR-141-3p associated with poor prognosis was detected in NPC patients. Moreover, overexpression of miR-141-3p promoted cell proliferation, migration, and invasion in NPC cells. It was also found that miR-141-3p promoted EMT and activated the mTOR signaling pathway in NPC. Furthermore, DLC1 was indicated as a direct target of miR-141-3p and miR-141-3p negatively correlated with DLC1 expression in NPC. In particular, upregulation of DLC1 could impair the promoted effect of miR-141-3p in NPC. CONCLUSIONS: MiR-141-3p promotes the progression of NPC by targeting DLC1 and activating the mTOR pathway.

[A nested case-control study of cruciferous vegetables intake, urinary isothiocyanates level and lung cancer risk among men in urban Shanghai].

Objective: To investigate the association between consumption of cruciferous vegetables (CV), level of urinary isothiocyanates (ITC) and the risk of lung cancer among man in urban Shanghai. Methods: A nested case-control study was conducted within the Shanghai Men's Health Study. Using incidence density sampling with a 2∶1 control to case selection ratio, 885 controls were selected to match 443 lung cancer cases diagnosed prior December 31, 2010. A food-frequency questionnaire was administered to estimate CV consumption. The high performance liquid chromatography method was applied to measure urinary ITC level. The CV intake and urinary ITC level were divided into quartiles according to distribution of control group. The lowest quartile was as a reference group. Conditional logistic regression model was used to analyze the relationship between CV intake, urinary ITC level and the risk of lung cancer. Results: The cruciferous vegetables intake median (P(25), P(75)) in cases and controls were 80.05 (46.89, 129.04) and 97.68 (55.25, 151.72) g/d (Z=-3.93, P<0.001). The urinary ITC level were 1.256 (0.474, 3.836) and 1.244 (0.484, 3.004) µmol/g Cr (Z=-0.39, P=0.697). After adjusting for potential confounding factors such as age, education level, smoking and alcohol consumption, for urinary ITC level, the OR(95%CI) for the highest quartile(≥3.004 µmol/g Cr) was 1.25 (0.87-1.80) compared with the lowest quartile(<0.484 µmol/g). For CV intake, the OR(95%CI) for the highest quartile(≥151.71 g/d) was 0.66 (0.43-1.02) compared with the lowest quartile(<55.25 g/d). Conclusion: No association was found between the CV intake, urinary ITC level and lung cancer risk in men.

Cruciferous vegetables intake and the risk of colorectal cancer: a meta-analysis of observational studies.

BACKGROUND: Epidemiological studies have reported inconsistent associations between cruciferous vegetable (CV) intake and colorectal cancer (CRC) risk. To our knowledge, a comprehensive and quantitative assessment of the association between CV intake and CRC has not been reported. METHODS: Relevant articles were identified by searching MEDLINE. We pooled the relative risks (RR) from individual studies using a random-effect model and carried out heterogeneity and publication bias analyses. RESULTS: Twenty-four case-control and 11 prospective studies were included in our analysis. When all studies were pooled, we yielded a significantly inverse association between CV (RR: 0.82; 95% confidence interval 0.75-0.90) intake and CRC risk. Specific analysis for cabbage and broccoli yielded similar result. When separately analyzed, case-control studies of CV intake yield similar results, and the results from the prospective studies showed borderline statistical significance. Moreover, significant inverse associations were also observed in colon cancer and its distal subsite both among prospective and case-control studies. CONCLUSIONS: Findings from this meta-analysis provide evidence that high intake of CV was inversely associated with the risk of CRC and colon cancer in humans. Further analysis on other specific CV, food preparation methods, stratified results by anatomic cancer site, and subsite of colon cancer should be extended in future study.

Mutations in the beta-myosin heavy chain gene in southern Chinese families with hypertrophic cardiomyopathy.

In this study, 14 unrelated hypertrophic cardiomyopathy (HCM) probands were scanned by polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing. Three mis-sense mutations of the beta-myosin heavy chain gene, MYH7, were found: valine (Val) 606 methionine (Met), arginine (Arg) 694 leucine (Leu), and Arg 723 glycine (Gly). All are reported here for the first time in Chinese subjects. The results showed that: Val606Met is an intermediate malignancy mutation; Arg694Leu is a novel mutation with a benign phenotype; and the Arg723Gly mutation is linked to malignancy - it can lead not only to HCM but also to dilated cardiomyopathy at various ages. The clinical symptoms associated with Arg723Gly emerged early and caused more severe clinical manifestation and poorer prognosis in females than in males. Mis-sense mutations were not detected in the myosin binding protein C, cardiac, cardiac troponin T type 2, or cardiac troponin I type 3 genes. The MYH7 gene may be an HCM mutation hotspot in the Chinese and have unique features in this study population.

Mesenchymal stem cells as a gene delivery system to create biological pacemaker cells in vitro.

Pacemaker cells differ from common cardiomyocytes due to the presence of a spontaneous depolarization process during the diastolic phase of the cardiac cycle. This is due to hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are responsible for providing an inward current. Genetically engineered mesenchymal stem cells (MSCs) were transfected with hHCN4 genes using lentiviral transfection, and their potential use as biological pacemaker cells was investigated. In addition to expressing an anticipated high level of the hHCN4 gene, MSCs transfected with hHCN4 genes also expressed characteristic hHCN4 protein, a cardiac pacemaker-like current and were capable of increasing the spontaneous beating rate of co-cultured cardiac myocytes. Control MSCs did not exert these effects. It is hypothesized that genetically engineered MSCs transfected with hHCN4 genes by lentiviral transfection can be modified to be cardiac pacemaker cells in vitro.

Csa-19, a radiation-responsive human gene, identified by an unbiased two-gel cDNA library screening method in human cancer cells.

A novel polymerase chain reaction (PCR)-based method was used to identify candidate genes whose expression is altered in cancer cells by ionizing radiation. Transcriptional induction of randomly selected genes in control versus irradiated human HL60 cells was compared. Among several complementary DNA (cDNA) clones recovered by this approach, one cDNA clone (CL68-5) was downregulated in X-irradiated HL60 cells but unaffected by 12-O-tetradecanoyl phorbol-13-acetate, forskolin, or cyclosporin-A. DNA sequencing of the CL68-5 cDNA revealed 100% nucleotide sequence homology to the reported human Csa-19 gene. Northern blot analysis of RNA from control and irradiated cells revealed the expression of a single 0.7-kilobase (kb) messenger RNA (mRNA) transcript. This 0.7-kb Csa-19 mRNA transcript was also expressed in a variety of human adult and corresponding fetal normal tissues. Moreover, when the effect of X- or fission neutron-irradiation on Csa-19 mRNA was compared in cultured human cells differing in p53 gene status (p53-/- versus p53+/+), downregulation of Csa-19 by X-rays or fission neutrons was similar in p53-wild type and p53-null cell lines. Our results provide the first known example of a radiation-responsive gene in human cancer cells whose expression is not associated with p53, adenylate cyclase or protein kinase C.

Rodent cell transformation and immediate early gene expression following 60-Hz magnetic field exposure.

Some epidemiological studies suggest that exposure to power frequency magnetic fields (MFs) may be associated with an elevated risk of human cancer, but the experimental database remains limited and controversial. We investigated the hypothesis that 60-Hz MF action at the cellular level produces changes in gene expression that can result in neoplastic transformation. Twenty-four hour 200 microT continuous MF exposure produced negative results in two standard transformation systems (Syrian hamster embryo cells and C3H/10T1/2 murine fibroblasts) with or without postexposure to a chemical promoter. This prompted a reexamination of previously reported MF-induced changes in gene expression in human HL60 cells. Extensive testing using both coded and uncoded analyses was negative for an MF effect. Using the same exposure conditions as in the transformation studies, no MF-induced changes in ornithine decarboxylase expression were observed in C3H/10T1/2 cells, casting doubt on a promotional role of MF for the tested cells and experimental conditions.

Menstrual blood loss, haemoglobin and ferritin concentration of Beijing women wearing steel ring, VCu 200, and TCu 220c IUDs.

Menstrual blood loss (MBL), serum ferritin and whole blood cyanmethemoglobin were measured at pre- and 1, 3, 6, 12, 18 and 24th postinsertion cycles in 60 women wearing the Steel Ring, the Copper V (VCu 200) or the Copper T (TCu 220c). The MBL, incidence of menorrhagia and iron deficiency anemia were lower among users of the Steel Ring than among users of the Copper V and T. Anemia occurred later and the duration of menstruation was shorter with the Steel Ring than with the Copper T. There were no statistically significant differences between the Copper V and T.

PIP: The effects of the Steel Ring, the Copper V (VCu 200), and the Copper T (TCu 220c) were compared in terms of menstrual blood loss, serum ferritin, the incidence of menorrhagia, and anemia before and after insertion to evaluate the safety of these IUDs and to determine if any of them are appropriate for longterm use in Chinese women. 60 healthy women, 20-39 years, with regular menstrual periods, normal pelvic examination, who had used no oral contraceptives (OCs) for more than 1 year were recruited. Those who previously had used an IUD or had an abortion or parturition were admitted after at least 3 normal menses. Each subject was instructed in the method for complete collection of menstrual blood for 1 entire menstrual period. Menstrual blood loss was measured by alkaline hematin photometry and a Stomacher Lab-blender was used for extraction. The insertions of the IUDs were uneventful. After insertion, the mean blood loss for each group at all intervals was significantly higher than that of preinsertion, especially in the 1st postinsertion cycle. Thereafter, blood loss remained high or gradually decreased, but it did not return to the preinsertion levels even at the 24th postinsertion cycle. The differences were still significant, especially for the T group. The mean increase 25.4 ml (55.8%) for the Ring group, 32.3 ml (56.8%) for the V group, and 39.9 ml (82.2%) for the T group. The highest blood loss for the Ring group was 154 ml, for the V group 290.9 ml, and for the T group 211 ml. The incidence of menorrhagia of all IUDs was significantly increased in the 1st postinsertion cycle. Except for the Ring group, the differences were still significant even in the 24th postinsertion cycle. The mean value of serum ferritin for the Ring group was significantly decreased at the 18 and 24th postinsertion cycles. For the V group, the mean value decreased significantly at the 6, 12, and 18th postinsertion cycles and was below the normal level (16 ng/ml). For the T group, the mean value decreased significantly at the 12th and 18th postinsertion cycles, but the difference was not significant at the 24th postinsertion cycle as compared with preinsertion in either the V or T groups. After insertion, the mean hemoglobin (Hb) concentrations were still above 12 gm/dl in each cycle, but the incidence of Hb less than 12 gm/dl, which was zero before insertion in all groups, for the Ring group was 12.5% and 6.2% at the 12 and 24th postinsertion cycles and for the V group, 10% at the 1st postinsertion cycle, then gradually increased to 21.1% at the 24th postinsertion cycle. Menstrual flow was significantly prolonged only in the T group. This study indicated that blood loss, incidence of menorrhagia, and iron deficiency anemia were lower among Steel Ring users than among VCu 200 and TCu 220c users.

A randomized comparative clinical evaluation of the Steel Ring, the VCu200 and the TCu220c IUDs.

A randomized comparative clinical study of the Steel Ring, VCu200 and TCu220c IUDs was carried out in Beijing. Six-hundred subjects were recruited and each group of 200 was inserted with one of the three devices. The TCu220c and the VCu200 had statistically significantly lower pregnancy and expulsion rates at one and two years of use than the Steel Ring. However, the Steel Ring consistently had the lowest rate of removal for pain and/or bleeding. At two years, the early differences of use-related discontinuation and continuation between the higher rates of the Steel Ring and the lower rates of the VCu200 and TCu220c were significantly reduced. There were no statistically significant differences of net event rates between VCu200 and TCu220c.

PIP: This comparative study evaluated the acceptability and effectiveness of 3 IUDs--the Steel Ring, the V-shaped Copper 200 (VCu200), and the T-shaped Copper 200c (TCu200c)--in parous Chinese women. 200 healthy women 20-39 years of age were randomly allocated to each of the 3 treatment groups. All subjects had had at least 1 full-term pregnancy. The TCu200c and VCu200 performed significantly better than the Steel Ring in terms of pregnancy and expulsion rates, at both the 1 and 2-year follow up; however, the latter device had significantly lower rates of removal for pain and bleeding. At 2 years, there had been 14 pregnancies in women using the Steel Ring, 6 in VCu200 users, and 2 in users of the TCu200c device; expulsions totalled 25, 3, and 7, respectively. Total use-related discontinuations at 2 years were 42, 28, and 34, respectively, among users of these 3 IUDs. Further evaluation will be conducted after 5 years of continuous use.