The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

Abstract Background Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown. Methods We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot. Results We found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes. Conclusions Our findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy

Tissue-specific and stereoselective accumulation of Dechlorane Plus isomers in two predator fish in a laboratory feeding study

The tissue-specific bioaccumulation of Dechlorane Plus (DP) isomers was investigated in two predator fish species (redtail catfish, RF; and oscar fish, OF) that were feeding on tiger barb (TB), which was exposed to syn-DP and anti-DP isomers. The biotransformation potential of DP isomers was examined by in vitro metabolism using fish liver microsomes. No difference in accumulation behaviors of DP isomers was observed between RF and OF, and the accumulation of both syn- and anti-DP isomers exhibiting a linear increase trend with the exposure time in all fish tissues. The assimilation efficiencies and depuration rates for syn-DP and anti-DP were determined to be the highest in the liver. Biomagnification factors (BMFs) for both syn-DP and anti-DP were higher than one in the serum and gastrointestinal tract of fish, whereas were less than one in the other tissues. The wet-weight concentrations of DP isomers in tissues were significantly correlated with the lipid contents in both fish species, indicating that the tissue distribution of DP isomers occurred through passive diffusion to the lipid compartments in vivo. Tissue-specific compositions of DP isomers were observed, with anti-DP selectively accumulating in the liver, gonad, serum, and gills, whilst syn-DP in the carcass and GI tract. However, after being normalized of all tissues, the fish showed no selective accumulation of DP isomers during the exposure period, and selective accumulation of syn-DP was observed during the depuration period. No potential DP metabolites were detected in the fish tissues and in vitro metabolism systems. The main cause of this stereoselective DP isomer accumulation could have been the selective excretion of anti-DP isomer through the fish feces

Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice

Background: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models. Methods: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group. Results: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 109/L at the 28th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF4:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28th day, particularly those injected with 1.5 mg/kg NaYbF4:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney. Conclusion: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice

Additional file 5: of The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

Figure S2. (a) H&E-stained paraffin-embedded sections obtained from xenografts established by subcutaneous transplantation with sh-con and sh-PTTG3P HepG2 cells 4 weeks after cell injection. (b) H&E-stained paraffin-embedded sections obtained from xenografts established by subcutaneous transplantation with Lv-con and Lv-PTTG3P HepG2 cells 4 weeks after cell injection. (c) Representative images of PTTG3P expression from tumor xenografts established by subcutaneous transplantation with sh-con and sh-PTTG3P HepG2 cells by ISH assays. (d) Representative images of PTTG3P expression from tumor xenografts established by subcutaneous transplantation with Lv-con and Lv-PTTG3P HepG2 cells by ISH assays. (TIF 9470 kb

Additional file 1: of The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

Table S1. Sequences of primers and shRNA used in this study. (DOCX 29 kb

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study

ABSTRACT Objectives: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. Materials and Methods: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. Results: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p 0.80], indicating a robust correlation. Conclusions: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC

Additional file 2: of The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

Table S2. The raw data for microarry analysis in 3 HCC tumor tissues and adjacent normal tissues. (XLS 13300 kb

Additional file 3: of The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

Figure S1. (a) Taking the differentially expressed mRNAs in our microarray analysis as input, the pathway analysis revealed that cell cycle was the most affected biological process. (b) The level of PTTG3P in LO2, HepG2, Huh7, MHCC-97H, SMMC-7721, QGY7701, SK-Hep1 and Hep3B cells was evaluated by qRT-PCR. Relative high levels of PTTG3P were observed in Hep3B cells while relative low levels were found in HepG2 cells. U6 was used as a housekeeping gene. (TIF 4460 kb

Additional file 4: of The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

Table S3. A list of top differentially expressed lncRNAs in microarray analysis. (DOCX 41 kb