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OBJECTIVE: The aim of this study was to investigate whether microRNA-421 could participate in the proliferative, migratory and inflammatory changes of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis by targeting SPRY1. PATIENTS AND METHODS: The expressions of microRNA-421 and SPRY1 in synovial tissues and FLS were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. The binding condition between microRNA-421 and SPRY1 was verified by the Dual-Luciferase reporter gene assay. MicroRNA-421 mimics and inhibitor were constructed and transfected. The levels of extracellular interleukin-1 (IL-1), IL-6, and COX2 in FLS after microRNA-421 mimics or inhibitor transfection were detected by enzyme-linked immunosorbent assay (ELISA). The regulatory effect of microRNA-421 on the proliferation and migration of FLS was detected using cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, collagen-induced RA mouse model was constructed to confirm the specific effect of microRNA-421 on regulating RA development. RESULTS: MicroRNA-421 was highly expressed in the synovial tissues of RA patients. SPRY1 expression in FLS was negatively regulated by microRNA-421. Moreover, the overexpression of microRNA-421 significantly promoted proliferative, invasive potentials and inflammatory response of FLS. In vivo, RA mouse model indicated that downregulated microRNA-421 and upregulated SPRY1 were observed in mice injected with cortisone and microRNA-421 inhibitor when compared with those of controls. CONCLUSIONS: MicroRNA-421 promotes the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by downregulating the SPRY1 expression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We aim to investigate the expression of long non-coding RNALINP1 (lncRNA LINP1) in prostate cancer (PCa) and its potential mechanism. PATIENTS AND METHODS: The expression of lncRNA LINP1 in 74 pairs of PCa and normal tissues were detected by quantitative Real- time polymerase chain reaction (qRT-PCR); the relationship between its expression and the pathological features and prognosis of PCa was also analyzed. The expression of lncRNA LINP1 in the PCa cell line was verified by qRT-PCR. Knockdown of LINP1 was constructed by transfection of small interfering RNA (siRNA) in two PCa cell lines (Lncap and PC-3). The biological function of LINP1 was evaluated by cell counting kit-8 (CCK-8) assay, colony formation assay, migration and invasion assay, respectively. Finally, the potential mechanism of LINP1 was explored by Western blot and qRT-PCR. RESULTS: qRT-PCR results showed a higher expression of LINP1 in PCa than that of normal tissues. Compared with PCa patients with a lower expression of LINP1, those with higher expression had a higher tumor stage, lymphatic metastasis and distant metastasis rate, and lower overall survival rate. Proliferation, invasion and metastasis in cells transfected with si-LINP1 were remarkably decreased than those transfected with negative control (si-NC). Moreover, the expressions of the key proteins in the p53 signaling pathway, including p53, PTEN, Akt and CDK2 were remarkably decreased in cells after knockdown of LINP1. In addition, a negative correlation between LINP1 and p53 was confirmed by rescue experiments. CONCLUSIONS: Up-regulated LINP1 in PCa was correlated with a higher PCa stage, lymphatic metastasis, distant metastasis, and worse prognosis. Furthermore, LINP1 could promote the proliferative, migratory and invasive abilities of PCa by regulating the p53-signaling pathway. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease, whereas its cause still remains elusive. Typical pathological manifestations of RA include persistent synovitis and bone degeneration in the surrounding joints. Although the incidence of RA is high in population, currently there have been no effective cures for it. The purpose of this study is to investigate the therapeutic effects and main mechanism of IKKε (inhibitor of nuclear factor kappa-B kinase ε) in collagen II induced-Rheumatoid Arthritis (CIA) mice model. MATERIALS AND METHODS: IKKε-/- and wild-type (WT) littermate control mice were intraperitoneally injected with 5 mg/kg collagen II monoclonal antibody cocktail (Cab) for 5 days. After that, the nociception threshold and clinical rheumatoid arthritis articular damage score of mice were evaluated. After 5 days-CAb treatment, serum levels of a series of inflammatory cytokines including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and interferon (IFN) were detected with enzyme-linked immunosorbent assay (ELISA) in both groups. Besides, Real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) was used to evaluate the expression of these inflammatory cytokines in plantar tissues. In addition, Western blot was performed to investigate the protein levels of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B) signaling pathway. Moreover, WT mice receiving CAb were further applied with or without IKK inhibitor amlexanox (25 mg/kg) to investigate the expression of the above-mentioned inflammatory cytokines. RESULTS: Our work showed that IKKε-/- mice with CIA displayed less nociception and suppressed inflammatory response than WT mice. Meanwhile, the clinical rheumatoid arthritis articular damage scores were significantly decreased in IKKε-/- mice. The levels of TNF-α, IL-1β, IL-6 in serum and plantar tissues in IKKε-/- mice were significantly lower than those in WT mice. Besides, NF-κB expression in IKKε-/- mice was significantly decreased. Similarly, the same phenotype was observed in WT mice administrated with IKKε inhibitor amlexanox as that of IKKε-/- mice, indicating that inflammatory and nociception responses were remarkably decreased than those of the negative controls. CONCLUSIONS: IKKε plays an important role in promoting nociception and inflammatory response in CIA. Our research demonstrated that knockout of IKKε may serve as a new direction for clinical prevention and treatment of rheumatoid arthritis. IKKε inhibitor amlexanox may become a new drug for the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Intrauterine glucocorticoid (GC) exposure is associated with disturbances in feto-placental growth. This study aimed to investigate whether folic acid supplementation can prevent dexamethasone (Dex)-induced feto-placental growth restriction. MATERIALS AND METHODS: Female C57BL/6J mice were subject to four different treatments, respectively: normal drinking water plus saline injection (NN), normal drinking water plus Dex injection (ND), drinking water supplemented with folic acid plus saline injection (FN), and drinking water supplemented with folic acid plus Dex injection (FD). Folic acid (100 μg/L) was administrated since 2 weeks before the mating and throughout pregnancy. Dex injection (100 μg/kg·d) was performed from E12.5 to E16.5. The placentas were collected at E17.5. RESULTS: The parameters including placental and fetal weight, the maximum placental diameter, volume of junctional and labyrinthine zones, and vascular density in the ND group were significantly smaller compared to the NN group. Except the maximum placental diameter, each of the above parameters in the FD group was significantly larger compared to the ND group.The levels of glucocorticoid receptor (GR) protein, and endothelial growth factor A, C (VEGFA, VEGFC) and placental growth factor (PIGF) mRNAs were significantly lower in the ND group compared to NN group. The VEGFA and PIGF mRNA level in the FD group was significantly higher than that in the ND group, as well as VEGFA and VEGFC protein level. CONCLUSIONS: Folic acid may attenuate Dex-induced restriction on placental growth by elevating the expression of VEGFA and PIGF, and further raising vascular density. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Long non-coding RNA LINP1 promotes the malignant progression of prostate cancer by regulating p53" by H.-F. Wu and others which appeared in the 2018 issue.