ABSTRACT
BACKGROUND: Although papillary thyroid carcinoma (PTC) has a favorable prognosis, it could affect patient life quality and become a serious threat because of invasion and metastasis. Many investigations have suggested that circular RNAs (circRNAs) are involved in different cancer regulations. Nevertheless, circRNAs role in invasive PTC remains unclear. METHODS: In the present investigation, next-generation sequencing was applied to explore abnormal circRNA expression. The expression of circRNA phosphoglycerate dehydrogenase (circPHGDH) in PTC cell lines and tissues were examined. Then, we investigated regulatory mechanism and circPHGDH downstream targets using bioinformatics analysis and luciferase reporting analysis. Then transwell migration, Cell Counting Kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used for cells migration and proliferation analysis. In vivo metastasis and tumorigenesis assays were also employed to evaluate the circPHGDH role in PTC. RESULTS: The data showcased that circPHGDH expression increased in both PTC cell lines and tissues, which suggested that circPHGDH functions in PTC progression. circPHGDH downregulation suppressed PTC invasion and proliferation in both in vivo and in vitro experiments. Bioinformatics and luciferase reporter results confirmed that both microRNA (miR)-122-5p and pyruvate kinase M2 subtype (PKM2) were downstream targets of circPHGDH. PKM2 overexpression or miR-122-5p suppression reversed PTC cell invasion and proliferation post silencing circPHGDH by restoring aerobic glycolysis. CONCLUSION: Taken together, our research found that circPHGDH downregulation reduced PTC progression via miR-122-5p/PKM2 axis regulation mediated by aerobic glycolysis.
Subject(s)
Cell Proliferation , Disease Progression , Down-Regulation , Membrane Proteins , MicroRNAs , Phosphoglycerate Dehydrogenase , RNA, Circular , Thyroid Cancer, Papillary , Thyroid Neoplasms , Animals , Female , Humans , Male , Mice , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasm Invasiveness , Phosphoglycerate Dehydrogenase/genetics , RNA, Circular/genetics , RNA, Circular/metabolism , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/metabolism , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , Pyruvate Kinase/genetics , Pyruvate Kinase/metabolismABSTRACT
OBJECTIVE: To investigate the chemical constituents from the stems of Schisandra sphaerandra. METHOD: Compounds were isolated from ethanolic extract of the titled herb by silica gel column chromatography, and their structures were elucidated by physical and chemical evidences and spectroscopic analysis. RESULT: 12 compounds were obtained and identified as wuweizisu C (1), ganwuweizic acid (2), nigranoic acid (3), catechin (4), 2 alpha,24-dihytroxyursolic acid. (5), 3 beta-O-acetylursolic acid (6), ursolic acid (7), slyceryl 26-hydroxyhexacosanoate (8), slyceryl hexacosanoate (9), fat acids (10), beta-sitosterol (11), daucosterol (12), respectirely. CONCLUSION: Three pentacyclic triterpene carboxylic acid (5-7) were isolated from Schisandreae for the first time.