ABSTRACT
OBJECTIVE: The aim of this study was to investigate the role of long non-coding Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in bladder cancer (BCa), and the mechanism of OIP5-AS1/microRNA-217 (miR-217)/metadherin (MTDH) in promoting the progression of BCa. PATIENTS AND METHODS: OIP5-AS1, miR-217 and MTDH expressions in BCa tissues and cells were detected by qRT-PCR or Western blot. CCK-8 and transwell assays were used to determine the proliferation and invasion of BCa cells. The correlation between OIP5-AS1 and miR-217, miR-217 and MTDH, and OIP5-AS1 and MTDH were studied by Luciferase reporter assay and Spearman correlation analysis. Statistical analysis of test data was performed using t-test. RESULTS: OIP5-AS1 was upregulated in BCa tissues and cells, and OIP5-AS1 knockdown could inhibit the proliferation and invasion of BCa cells. MiR-217 was a direct-acting target of OIP5-AS1, and MTDH was a target of miR-217. OIP5-AS1 knockdown inhibits human BCa cell proliferation and invasion through miR-217/MTDH axis. CONCLUSIONS: This study systematically explored the effect of OIP5-AS1 in human BCa. MiR-217/MTDH pathway mediated the promotion of OIP5-AS1 in BCa cells proliferation and invasion. OIP5-AS1, as an oncogene, could be used as a biomarker for the treatment of BCa.
Subject(s)
Membrane Proteins/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , RNA-Binding Proteins/metabolism , Urinary Bladder Neoplasms/metabolism , Cell Proliferation , Cells, Cultured , Humans , Membrane Proteins/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , RNA-Binding Proteins/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
OBJECTIVE: In cervical carcinoma (CC), microRNAs (miRNAs) were reported to be involved in its development. In this study, we explored how miR-377-3p regulates cell metastasis and epithelial-mesenchymal transition (EMT) in CC. PATIENTS AND METHODS: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), Dual-Luciferase Assay, transwell assays, and Western blot analysis were performed to explore the dysregulation of miR-377-3p. RESULTS: MiR-377-3p expression was decreased in CC, and the downregulation of miR-377-3p could predict poor prognosis in CC patients. Moreover, miR-377-3p overexpression repressed cell invasion and migration in CC. Similarly, miR-377-3p overexpression also inhibited EMT in CC cells. Furthermore, miR-377-3p directly targeted SGK3 in CC cells. SGK3 silence had the same function as miR-377-3p overexpression in CC. Especially, the upregulation of SGK3 abolished the inhibitory action of miR-377-3p in CC. CONCLUSIONS: Taken together, miR-377-3p inhibited cell metastasis and EMT by suppressing SGK3 expression. Moreover, the high miR-377-3p expression could predict good prognosis of CC patients.
Subject(s)
Epithelial-Mesenchymal Transition/physiology , MicroRNAs/biosynthesis , Protein Serine-Threonine Kinases/biosynthesis , Uterine Cervical Neoplasms/metabolism , Adult , Female , HEK293 Cells , HeLa Cells , Humans , MicroRNAs/genetics , Middle Aged , Protein Serine-Threonine Kinases/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathologyABSTRACT
High-mobility group box 1 (HMGB1) proteins are substantially up-regulated in acute and chronic hepatitis. However, the immunopathogenic role of HMGB1 in patients with chronic hepatitis B (CHB) has not been elucidated. In this study, using a cohort of 36 CHB patients, we demonstrated a crucial role for HMGB1 to modulate balance between regulatory T (Treg) and T helper 17 (Th17) cells via the toll-like receptor (TLR)-4-interleukin (IL)-6 pathway. Serum HMGB1 levels were dramatically higher in CHB patients and increased along with liver injury, inflammation and fibrosis. Notably, HMGB1 increased along with decreased Treg/Th17 cells ratios in the periphery or intrahepatic microenvironment, which provides a clue for HMGB1 to favour Th17 responses whereas inhibit Treg responses. For in vitro studies, serum pools were constructed with serum from CHB patients at an advanced stage, whereas peripheral blood mononuclear cells (PBMC) pools were constructed with cells from those at an early stage. CHB-serum significantly enhanced retinoic acid-related orphan receptor-γt (RORγt), whereas they inhibited forkhead box P3 (Foxp3) expression in CHB-PBMC, which could be reversed by blocking of HMGB1, TLR4, or IL-6. Besides, recombinant HMGB1 (rHMGB1) dose-dependently up-regulated RORγt whereas down-regulated Foxp3 expression in CHB-PBMC, and meanwhile, rHMGB1 enhanced TLR4 and IL-6 expression in CHB-PBMC. Moreover, the axis of HMGB1-TLR4-IL-6-Treg/Th17 required noncontact interactions between CD4 and non-CD4 cells. In addition, rHMGB1 down-regulated anti-inflammatory proteins on CD4(+) CD25(+) cells whereas up-regulated pro-inflammatory cytokines in CD4(+) CD25(-) cells. In summary, enriched HMGB1 in CHB patients shifts Treg/Th17 balance to Th17 dominance via the TLR4-IL-6 pathway, which exacerbates liver injury and inflammation.
Subject(s)
HMGB1 Protein/immunology , Hepatitis B, Chronic/immunology , Interleukin-6/immunology , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Toll-Like Receptor 4/immunology , Adult , Cohort Studies , Female , HMGB1 Protein/blood , Hepatitis B, Chronic/pathology , Humans , Liver/immunology , Liver/pathology , Liver Cirrhosis/pathology , Male , Middle Aged , Young AdultABSTRACT
Sesquiterpenoids are a group of naturally occurring 15-carbon isoprenoid compounds that are mainly found in higher plants, microorganism and marine life. Many of them provided encouraging leads for chemotherapeutics. In this review, the sesquiterpenoids are classified according to the ring numbering system and the functional groups presented in the core structures as acyclic, mono-, bi-, and tricyclic derivatives, and a current overview of sesquiterpenoids as potential cytotoxic anticancer agents is provided.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biological Products/chemistry , Biological Products/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Animals , Cytotoxins/chemistry , Cytotoxins/pharmacology , Humans , Neoplasms/drug therapyABSTRACT
OBJECTIVE: To investigate the safety and pharmacokinetics of bromotetrandrine (BrTet, W198), a novel inhibitor of P-glycoprotein (P-gp), after single-dose i.v. infusion in healthy Chinese volunteers. METHODS: We conducted a randomized, dose-escalating, phase I clinical study for that purpose. Thirty healthy subjects received BrTet at the doses of 10, 20 or 30 mg/m(2) by i.v. infusion. Plasma and urine concentrations of bromotetrandrine were determined by using a liquid chromatography-tandem mass spectrometric (LC/MS/MS) method. AUC was calculated by the trapezoidal rule extrapolation method. C(max), T(max), t(1/2alpha), t(1/2beta), Cl and V(d) were compiled from the plasma concentration-time data. RESULTS: Bromotetrandrine was generally well tolerated at all doses. No serious or severe adverse events were found in the study. The pharmacokinetic parameters of BrTet after single i.v. infusion doses of BrTet 10, 20 and 30 mg/m(2) were as follows: T(max) were 1.5 h in three groups, C(max) were 24.79, 39.59 and 64.31 microg/L, t(1/2alpha) were 0.37, 0.29 and 0.30 h, t(1/2beta) were 62.88, 56.45 and 52.20 h. AUC(0-194h) were 345.83, 688.15 and 1096.28 microg h/L, Cl were 23.68, 25.69 and 25.66 L h/m(2), V(d) were 157.73,156.96 and 140.73 L/m(2). In urine, the total eliminate rate of originate compound was 0.61 +/- 0.19%. CONCLUSIONS: This study suggested that bromotetrandrine was well tolerated in healthy volunteers within the dose range evaluated. The pharmacokinetics parameters of bromotetrandrine indicated that the compound was rapidly distributed and accumulated in the tissues, and slowly cleared from plasma, which supported the use of BrTet for a once or twice dosing per chemotherapy cycle.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/pharmacokinetics , Benzylisoquinolines/adverse effects , Benzylisoquinolines/pharmacokinetics , Adult , Antineoplastic Agents, Phytogenic/administration & dosage , Benzylisoquinolines/administration & dosage , China , Chromatography, High Pressure Liquid , Female , Half-Life , Humans , Infusions, Intravenous , Male , Metabolic Clearance Rate , Sex Characteristics , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , Young AdultABSTRACT
Two novel rearrangement products of the degradated derivative of maoecrystal A (1), an ent-kaurane-type diterpene via a Wagner-Meerwein process, have been reported.
Subject(s)
Diterpenes, Kaurane/chemistry , Diterpenes/chemistry , Magnetic Resonance SpectroscopyABSTRACT
A new C19-diterpenoid alkaloid, lasiansine (1), was isolated from the roots of Aconitu nagarum var. lasiandrum (Ranunculaceae) together with six known diterpenoid alkaloids. The structure of 1 was elucidated by spectral methods (1H-NMR, 13C-NMR, 2D-NMR, HRMS, IR), and the 13C-NMR spectrum of 16-epipyroaconine (3) and the single-crystal X-ray analysis of its derivative (5) are reported for the first time.
Subject(s)
Aconitum/chemistry , Diterpenes/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Plant Roots/chemistry , Plants, Medicinal/chemistry , Secologanin Tryptamine Alkaloids/chemistry , China , Chromatography , Diterpenes/isolation & purification , Heterocyclic Compounds, 4 or More Rings/isolation & purification , Molecular Structure , Secologanin Tryptamine Alkaloids/isolation & purification , SpectrophotometryABSTRACT
An attempt to enlarge the B ring of maoecrystal B (6), an ent-kaurane-type diterpene from Isodon eriocalyx (Labiatae), to obtain the desired compound 23 via six steps, led to the novel rearranged diterpene compound 22.
Subject(s)
Diterpenes, Kaurane/chemistry , Diterpenes/chemistry , Isodon/chemistry , Indicators and Reagents , Magnetic Resonance Spectroscopy , Mass Spectrometry , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
A novel norditerpenoid alkaloid, beiwudine (1), was isolated from the roots of Aconitum kusnezoffii. Its structure was established on the basis of chemical and NMR spectral studies.
