Long non-coding RNA PVT1 regulates glioma proliferation, invasion, and aerobic glycolysis via miR-140-5p.

The article "Long non-coding RNA PVT1 regulates glioma proliferation, invasion, and aerobic glycolysis via miR-140-5p, by Y. Shao, H.-T. Chen, Q.-R. Ma, Y.-W. Zhang, Y.-Q. He, J. Liu published in Eur Rev Med Pharmacol Sci 2020; 24(1): 274-283-DOI: 10.26355/eurrev_202001_19922-PMID: 31957841" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19922.

Long non-coding RNA PVT1 regulates glioma proliferation, invasion, and aerobic glycolysis via miR-140-5p.

OBJECTIVE: To investigate the regulation of long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) on proliferation, invasion, and aerobic glycolysis in glioma cells via miR-140-5p. PATIENTS AND METHODS: Sixty patients with glioma treated in our hospital were recruited. The expression of PVT1 in tissues and cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the effects on the prognosis were observed. Glioma cell lines U87 and T98MG were either stably or transiently transfected with over-expression or inhibition vectors. Cell counting kit-8 (CCK-8), transwell, glucose, and lactate detection were employed to measure cell proliferation, invasion, and aerobic glycolysis after transfection. The correlation between PVT1 and miR-140-5p was determined by Dual-Luciferase reporter assay. RNA pull-down and RNA immunoprecipitation (RIP) test were adopted to indicate the correlation between PVT1 and miR-140-5p. RESULTS: PVT1 was highly expressed and had superior diagnostic value in gliomas, and the high expression of PVT1 resulted in poor prognosis of patients. Over-expressing PVT1 increased cell proliferation, invasion, and aerobic glycolysis, while inhibiting PVT1 yielded opposite outcome. Dual-Luciferase reporter assay confirmed that PVT1 could target miR-140-5p. Functional analysis showed that over-expression of miR-140-5p inhibited proliferation, invasion, and aerobic glycolysis in glioma cells. Rescue experiment found that the inhibitory effect of miR-140-5p could be eliminated by up-regulating PVT1 expression. CONCLUSIONS: PVT1 promotes proliferation, invasion, and aerobic glycolysis in glioma cells by regulating miR-140-5p.

P2X3 receptor-mediated visceral hyperalgesia and neuronal sensitization following exposure to PTSD-like stress in the dorsal root ganglia of rats.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) often share co-morbidity with chronic pain conditions. Recent studies suggest a role of P2X3 receptors and ATP signaling in pain conditions. However, the underlying mechanisms of visceral hyperalgesia following exposure to PTSD-like stress conditions remain unclarified. METHODS: The behavior and hormones relevant for PTSD were studied. Visceromotor responses (VMR) and the abdominal withdrawal reflexes (AWR) to colorectal distention (CRD) were recorded to determine P2X3-receptor-mediated alteration of hyperalgesia following single-prolonged stress (SPS) exposure. Immunofluorescence, Western blotting, and patch-clamp were used. KEY RESULTS: The escape latency, adrenocorticotropic hormone and cortisol were increased on days 7-14. Visceromotor responses and AWR was reduced at day 1 in SPS rats but increased to higher levels than in controls after exposure to day 7. Intrathecal administration of the P2X3-receptor antagonist TNP-ATP abolished the CRD response. Based on immunofluorescence and Western blotting analysis, SPS-treated rats exhibited reduced P2X3 expression in dorsal root ganglia (DRG) after day 1 compared with controls. P2X3 expression in DRG was enhanced on day 7 after SPS and the increase of the P2X3 expression was maintained on day 14 and 21 compared with controls. The P2X3-receptor agonist α,ß-me ATP (10 µM) induced a fast desensitizing inward current in DRG neurons of both control and SPS-treated rats. The average peak current densities in SPS-treated group were increased 3.6-fold. TNP-ATP (100 nM) markedly blocked all fast α,ß-me ATP-induced inward currents in the DRG neurons both in control and SPS-treated rats. CONCLUSIONS & INFERENCES: The data indicate an important role of P2X3 signaling in visceral hyperalgesia following PTSD-like stress.

MicroRNA-185 regulates chemotherapeutic sensitivity in gastric cancer by targeting apoptosis repressor with caspase recruitment domain.

Gastric cancer remains the second leading cause of cancer deaths worldwide. Resistance to chemotherapy is a significant barrier for effective cancer treatment. Here, we identified miR-185 to be a contributor to chemosensitivity in gastric cancer. We observed low levels of miR-185 in gastric cancer cell lines and clinical tissues, compared with gastric epithelium cell line and noncancerous tissues. Furthermore, enforced expression of miR-185 increased the sensitivity of gastric cancer cells to low-dose chemotherapeutic agents, which alone cannot trigger significant apoptosis. Conversely, knockdown of endogenous miR-185 prevented high-dose chemotherapy-induced apoptosis. In elucidating the molecular mechanism by which miR-185 participated in the regulation of chemosensitivity in gastric cancer, we discovered that apoptosis repressor with caspase recruitment domain (ARC) is a direct target of miR-185. The role of miR-185 was confirmed in gastric tumor xenograft model. The growth of established tumors was suppressed by a combination therapy using enforced miR-185 expression and a low dose of anticancer drugs. Finally, we found that RUNX3 (Runt-related transcription factor) was involved in the activation of miR-185 at the transcriptional level. Taken together, our results reveal that RUNX3, miR-185 and ARC regulate the sensitivity of gastric cancer cells to chemotherapy.

Symptomatic diffuse esophageal spasm as a major ictal manifestation of post-traumatic epilepsy: a case report.

Post-traumatic epilepsy (PTE) can create diagnostic confusion when typical epileptic seizures are not manifest. Abdominal symptoms as a manifestation of PTE are rare in this setting. We present a 43-year-old female with paroxysmal chest and abdominal pain, nausea, salivation, and intermittent dysphagia. Esophageal testing demonstrated diffuse esophageal spasm, but smooth muscle relaxants provided no relief. Finally, after history revealed that a motor vehicle accident temporally preceded symptom onset, video electroencephalography confirmed PTE. Therapy with anti-epileptic drug completely resolved symptoms, and the esophageal motor pattern normalized. We speculate that abnormal epileptiform discharges from the seizure focus altered cerebral input to intrinsic esophageal innervation, resulting in inhibitory dysfunction and a picture resembling diffuse esophageal spasm. This is the first report of symptomatic esophageal spasm as a major ictal manifestation of PTE.

CYP1A2 is the major isoform responsible for paeonol O-demethylation in human liver microsomes.

1. Paeonol, the primary active component of a traditional Chinese medicine Moutan Cortex, has a wide range of pharmacological activities. In the present study, the metabolism of paeonol by cytochrome P450s (CYPs) was investigated in human liver microsomes. 2. One O-demethylated metabolite was detected in reaction catalysed by human liver microsomes, and was identified as resacetophenone by comparing the tandem mass spectra and the chromatographic retention time with that of the standard compound. 3. The study with a chemical selective inhibitor, cDNA-expressed human CYPs, a correlation assay, and a kinetics study demonstrated that CYP1A2 was the major isoform responsible for the paeonol O-demethylation in human liver microsomes.

Hydroxylation of tanshinone IIa in human liver microsomes is specifically catalysed by cytochrome P4502A6.

Tanshinone IIa, the primary active component of a traditional Chinese medicine Salvia miltiorrhiza (Danshen), has a wide range of pharmacological activities. In the present study, the metabolism of tanshinone IIa (5 microM) by cytochrome P450s (CYPs) was investigated in human liver microsomes. One mono-hydroxylated metabolite was detected in a reaction catalysed by human liver microsomes, and was identified as tanshinone IIb by comparing the tandem mass spectra and the chromatographic retention time with that of the standard compound. The study with a chemical selective inhibitor, cDNA-expressed human cytochrome P450s, correlation assay, and kinetics study demonstrated that CYP2A6 was the specific isozyme responsible for the hydroxyl metabolism of tanshinone IIa (5 microM) in human liver microsomes.

Mutation of GJB2 in a Chinese patient with keratitis-ichthyosis-deafness syndrome and brain malformation.

OBJECTIVE: Keratitis-ichthyosis-deafness syndrome (KID) is a rare congenital disorder. Mutations in the GJB2 gene have recently been identified as the causative mutations of KID. AIM: To define the GJB2 mutation in a Chinese patient with KID and brain malformation. METHODS: Genomic DNA was extracted from peripheral blood and used to amplify the GJB2 gene. Direct sequencing and endonuclease digestion were used for mutation analysis. RESULTS: We identified a heterozygous missense mutation (D50N) in the GJB2 gene in this patient. CONCLUSIONS: These results indicate that KID syndrome in this patient was caused by a dominant mutation of GJB2.

Characterization of triptolide hydroxylation by cytochrome P450 in human and rat liver microsomes.

Triptolide, the primary active component of a traditional Chinese medicine Tripterygium wilfordii Hook F, has a wide range of pharmacological activities. In the present study, the metabolism of triptolide by cytochrome P450s was investigated in human and rat liver microsomes. Triptolide was converted to four metabolites (M-1, M-2, M-3, and M-4) in rat liver microsomes and three (M-2, M-3, and M-4) in human liver microsomes. All the products were identified as mono-hydroxylated triptolides by liquid chromatography-mass spectrometry (LC-MS). The studies with chemical selective inhibitors, complementary DNA-expressed human cytochrome P450s, correlation analysis, and enzyme kinetics were also conducted. The results demonstrate that CYP3A4 and CYP2C19 could be involved in the metabolism of triptolide in human liver, and that CYP3A4 was the primary isoform responsible for its hydroxylation.

The alteration of PTEN tumor suppressor expression and its association with the histopathological features of human primary hepatocellular carcinoma.

PURPOSE: Although deletions or inactivating mutations of the tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome 10) are involved in the development of a variety of tumors including glioblastoma, melanoma, prostate cancer, breast cancer, endometrial cancers etc., the role of PTEN expression in human primary hepatocellular carcinoma (HCC) has not yet been clarified. The aim of this study is to investigate the involvement of PTEN mRNA and protein expression in HCC. METHODS: The level of PTEN mRNA expression in HCC specimens was analyzed by Northern blot. PTEN poly-clonal antibody was raised by immunizing New Zealand white rabbit with (His)(6)-tagged PTEN fusion protein and characterized by Western blot. The level of PTEN protein expression was determined by immunohistochemistry. The significance of PTEN in HCC was analyzed by comparing its expression level with the clinicopathological parameters of HCC patients. RESULTS: Four transcripts of PTEN mRNA at 5.5 kb, 4.4 kb, 2.4 kb, and 1.8 kb were detected in most para-carcinoma liver tissues, and the expression level of PTEN mRNA in carcinoma liver tissues was found to decrease significantly. The poly-clonal antibody raised against histidine-tagged fusion PTEN protein showed specific immuno-reactivity to PTEN protein. Using the specific poly-clonal antibody prepared and characterized by ourselves, we found that PTEN protein was significantly down-regulated in HCC tissues compared with paired para-carcinoma tissues. The protein expression of PTEN is negatively associated with the pathological grading and presence of cancer thrombus of HCC. CONCLUSIONS: Down-regulation of PTEN expression may play an important role in the development of HCC and the level of PTEN expression may be a potential adjuvant parameter in forecasting the progression and prognosis of HCC patients.