Circ_PSD3 promotes the progression of papillary thyroid carcinoma via the miR-637/HEMGN axis.

AIMS: In the present study, we aimed to uncover the potential functions of circular RNA (circRNA) pleckstrin and Sec7 domain containing 3 (circ_PSD3) in papillary thyroid carcinoma (PTC) development. MAIN METHODS: The abundance of circ_PSD3, PSD3 messenger RNA (mRNA), microRNA-637 (miR-637) and hemogen (HEMGN; EDAG-1) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was employed to measure cell cycle progression and cell apoptosis. Western blot assay was used to examine protein expression. The proliferation ability and motility of PTC cells were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays, respectively. The interaction between miR-637 and circ_PSD3 or HEMGN was tested by dual-luciferase reporter assay. Animal experiments were used to explore the role of circ_PSD3 in PTC progression in vivo. KEY FINDINGS: Circ_PSD3 was aberrantly up-regulated in PTC tumor tissues compared with adjacent normal tissues. Circ_PSD3 and HEMGN promoted the cell cycle progression, proliferation and metastasis and impeded the apoptosis of PTC cells. MiR-637 was a direct target of circ_PSD3, and miR-637 directly interacted with HEMGN mRNA in PTC cells. Circ_PSD3 silencing-induced effects in PTC cells were partly attenuated by the addition of anti-miR-637 or HEMGN overexpression plasmid. Circ_PSD3/miR-637/HEMGN regulated the activity of PI3K/Akt signal pathway in PTC cells. Circ_PSD3 silencing inhibited the tumor growth in vivo. SIGNIFICANCE: Circ_PSD3 promoted the progression of PTC through regulating miR-637/HEMGN axis and activating PI3K/Akt signaling. Circ_PSD3/miR-637/HEMGN signaling axis might be a potential target for PTC therapy.

[Expression of apoptosis related protein in transforming growth factors-beta signaling pathway and its effects on the cell apoptosis in the lung tissues after acute pulmonary embolism].

OBJECTIVE: To study the expression changes in apoptosis related protein in transforming growth factors-beta signaling pathway (ARTS) in the lung tissues in a rat acute pulmonary embolism (APE) model and its effects on cell apoptosis. METHODS: A rat APE model was reproduced. Samples of lung tissues were harvested at time points of 1, 8, 24 and 48 hours after APE. Healthy rats were used as control. The changes in mRNA level of ARTS were identified by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the changes in its protein level, and also Bcl-2, Bcl-xL, XIAP and H2Ax proteins, which were related with ARTS-mediated cell apoptosis, were determined by Western blotting. Immunohistochemical method was employed to study the distribution and expression changes in ARTS in the lung tissue before and after APE. Apoptotic cells in lung tissue sections were identified by the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method. RESULTS: At different time points, the mRNA levels and the protein levels of ARTS significantly increased in the lung tissues of rats with APE at 1 hour and 48 hours (P<0.05 or P<0.01). The immunohistochemical study showed that ARTS had low expression levels and could not be detected in the normal lung tissue, but it was up-regulated obviously at 48 hours after APE, mainly expressed in the bronchial epithelium and the lung alveolar epithelium. Apoptotic cells could be observed in the lung tissue by TUNEL after APE and at the same time when the lung tissue cells exhibited lower levels of the anti-apoptotic proteins Bcl-2, Bcl-xL, and XIAP, as compared with controls. Apoptosis level (as evaluated by H2Ax, apoptotic marker staining) in the lung tissue cells was obviously raised compared with controls (P<0.05 or P<0.01). CONCLUSION: The expression of ARTS is up-regulated after APE, and ARTS-mediated apoptosis plays an important role in the cell apoptosis of lung tissue.