Abstract. Progestin and adipoQ receptor family member III (PAQR3) is a regulator that negatively modulates the Ras/Raf/ MEK/ERK signaling cascade and the GPCR Gβγ subunit signaling pathway. The role of PAQR3 in hepatocellular carcinoma (HCC) has not been elucidated. The present study investigated the expression of PAQR3 and its prognostic value in primary HCC patients. Furthermore, the functional aspects of PAQR3 were also studied using an in vitro cell model. PAQR3 expression was examined in paired HCC and adjacent noncancerous tissues using real-time quantitative RT-PCR (62 pairs) and western blotting (26 pairs). We also analyzed PAQR3 expression in 132 additional HCC samples by immunohistochemistry. The functional impact of PAQR3 on the proliferation and colony formation of an HCC cell line was analyzed by transfecting cells with a full-length PAQR3 expression vector or siRNA targeting PAQR3. The expression of PAQR3 was significantly decreased in the cancer tissues. Clinicopathological analyses showed that the expression of PAQR3 was significantly correlated with expression of serum α-fetoprotein (AFP), mitotic count, tumor size, histological grade and recurrence. Notably, Kaplan-Meier survival curves revealed a correlation between decreased expression of PAQR3 and the poor prognosis of HCC patients. Multivariate analyses showed that PAQR3 expression is an independent prognostic marker for overall and disease-free survival of HCC patients. Furthermore, restoring PAQR3 expression in HCC cells significantly diminished Hep3B cell proliferation and colony formation. Silencing PAQR3 expression in hepatic normal cell line LO2 significantly enhanced cell growth. PAQR3 may play an important role in the progression of HCC and serve as a potential candidate for the targeted therapy of HCC.
Abstract. 15-lipoxygenase 2 (15-LOX-2) is lost or significantly reduced in prostate cancer. However, the regulation of 15-LOX-2 remains unclear. In this study, we independently cloned the 5' upstream promoter fragments of 15-LOX-2 gene. Target DNA fragments each were cloned into an expression vector containing luciferase reporter gene, which were called LF1(-1533/+87), LF2(-628/+87), LF3(-253/+87), LF4(-157/ +87), LF5(-33/+87), LF6(-253/+1), and LF7(-157/+1). Each of these individual promoter fragments was transfected into primary prostate epithelial cells and prostate cancer LNCaP cells. The promoter activity gradually decreased with progressive deletions from LF2 to LF4. A significant drop was noted in the LF5. LF6 and LF7 that did not contain the 87-bp region downstream the transcription start site (TSS) have significant luciferase activities similar to those of corresponding fragments (LF3 and LF4) that contain 87-bp region downstream the TSS. This suggests that the 125-bp region (-157 to -33) of LF4 is critical for the promoter activity of 15-LOX-2 in the primary prostate epithelial cells PrEC and cancer cells LNCaP. Moreover, we discovered a specific glucocorticoid receptor (GR) responsive element (GRE) in this key region. The luciferase activities of the LF4 and LF7 were decreased in the LNCaP cells co-transfected with GR (hGR· or hGRß) expression vectors. This inhibitory effect is reversed after treatments with dexamethasone or two specific GR inhibitors (siRNAs of GR and RU486). Results from this study suggest a 125-bp region (-157 to -33) is critical for the 15-LOX-2 promoter activity in prostate epithelial cells and cancer cells, which was significantly downregulated by GR via the GRE in this region.
Background Medical teams (MTs) online can provide comprehensive and rapid healthcare services to patients through doctors’ collaboration. The growth of MTs continues with their increasing popularity among doctors and patients, but there also exists some disbanded MTs, which would break the continuity of healthcare services. We aim to addressing this pressing issue by exploring effects of team diversity and leadership types on the team status (i.e. team disbandment). Specifically, we classify team diversity into separation diversity, variety diversity and disparity diversity, and leadership types based on the clinical titles include strong, equal and weak types. Methods A dataset of 1,071 MTs online were traced from the Good Doctor Online, a leading online health community (OHC) in China on January 10, 2018, and 206 teams disbanded after 3 months. Logistic regression and Maximize Likelihood Estimation were used to examine their effects. Results Our findings suggest that variety diversity related to the departments positively affected team disbandment, but disparity diversity referring to the clinical titles negatively affected team disbandment. Separation diversity in terms of the members’ attitude exerted a negligible influence on team disbandment. Although strong and equal leadership negatively influenced team disbandment, they strengthened the positive effect of variety diversity, suggesting the stable structure matching of strong/equal-type leadership and low department diversity, and the matching of weak-type leadership and high department diversity. Conclusion This study focuses on effects of leadership types and team diversity, and their pairwise combinations are obtained to effectively reduce the disbandment probability of medical teams in OHCs. It could help platforms, team founders, and all those connected with MTs positively deal with the team disbandment crisis. Theoretical and practical implications in OHCs and limitations were discussed.
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