scholarly journals Downregulated ADARB1 Facilitates Cell Proliferation, Invasion and has Effect on the Immune Regulation in Ovarian Cancer

Author(s):  
Wei Zhu ◽  
Zhijie Xu ◽  
Meiyuan Huang ◽  
Xiang Wang ◽  
Xinxin Ren ◽  
...  

Ovarian cancer (OC) is typically diagnosed at an advanced stage and poses a significant challenge to treatment and recovery. Rencently, Adenosine deaminase RNA-specific B1 (ADARB1), an adenosine-to-inosine (A-to-I) RNA-editing enzyme, has been found to play an essential role in the development of cancer. However, the specific function of ADARB1 in ovarian cancer is still not fully understood. Here, we investigated the effects of ADARB1 on OC biology. By conducting bioinformatics analyses of several public databases, we found significantly decreased ADARB1 expression in OC cells and tissues. Moreover, RT-PCR and western blot showed lower ADARB1 expression in OVCAR3, HO8910pm and A2780 OC cells compared to human normal ovarian epithelial cell IOSE. Cell proliferation assay and clone formation assay showed that overexpression of ADARB1 (ADARB1-OE) inhibited the proliferation of tumor cells. Wound healing and transwell assay indicated that ADARB1-OE could suppress OC cell invasion and metastasis. Kaplan-Meier methods revealed that the patients with low level of ADARB1 displayed poor prognosis. TISIDB databases were further used to analyze the roles of ADARB1 in tumor-immune system interactions in OC patients. Furthermore, ADARB1-OE down-regulated the expression of phosphorylated AKT. Combination of ADARB1-OE and AKT inhibitor MK2206 exerted stronger cell growth inhibition. Thus, our investigation demonstrated that low levels of ADARB1 might be a potential target in the tumorigenesis and prognostic evaluation of OC patients.

2021 ◽  
Author(s):  
Qingqing Lin ◽  
Wenchao Liu ◽  
Song Xu ◽  
Liping Sun

Abstract Background The effect of serum lipids on ovarian cancer is controversial. We conduct this study to evaluate the prognostic value of preoperative plasma lipid profile in patients with ovarian cancer. Methods The medical records of 156 epithelial ovarian cancer patients who underwent surgical resection in our department were retrospectively reviewed and analyzed. Serum lipids profiles, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-Ⅰ (apoA-Ⅰ), apolipoprotein B (apoB) and clinicopathologic data were analyzed. Cox proportional hazards regression analyses and Kaplan-Meier method were performed to evaluate the overall survival (OS) and progression-free survival (PFS). Results Multivariable Cox regression analysis found that preoperative higher LDL-C level was significantly associated with worse OS (HR 2.088, 95% CI 1.052–4.147, p = 0.035), whereas higher HDL-C level showed significant association with better PFS (HR 0.491, 95% CI 0.247–0.975, p = 0.042). Further Kaplan–Meier survival analysis demonstrated that OS was longer for patients with low levels of LDL-C (< 2.76 mmol/L) compared to those with high levels of LDL-C (≥ 2.76 mmol/L) (P = 0.028), and PFS was better for patients with high levels of HDL-C (≥ 1.19 mmol/L) compared to those with low levels of HDL-C (< 1.19 mmol/L) (P = 0.001). Conclusions Preoperative HDL-C and LDL-C levels are significant predictors of clinical outcome in patients with epithelial ovarian cancer.


2021 ◽  
Author(s):  
Qingqing Lin ◽  
Wenchao Liu ◽  
Song Xu ◽  
Liping Sun

Abstract Background: The effect of serum lipids on ovarian cancer is controversial. We conduct this study to evaluate the prognostic value of preoperative plasma lipid profile in patients with ovarian cancer.Methods: The medical records of 156 epithelial ovarian cancer patients who underwent surgical resection in our department were retrospectively reviewed and analyzed. Serum lipids profiles, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-Ⅰ (apoA-Ⅰ), apolipoprotein B (apoB) and clinicopathologic data were analyzed. Cox proportional hazards regression analyses and Kaplan-Meier method were performed to evaluate the overall survival (OS) and progression-free survival (PFS).Results: Multivariable Cox regression analysis found that preoperative higher LDL-C level was significantly associated with worse OS (HR 2.088, 95% CI 1.052-4.147, p = 0.035), whereas higher HDL-C level showed significant association with better PFS (HR 0.491, 95% CI 0.247-0.975, p = 0.042). Further Kaplan–Meier survival analysis demonstrated that OS was longer for patients with low levels of LDL-C (< 2.76 mmol/L) compared to those with high levels of LDL-C (≥ 2.76 mmol/L) (P = 0.028), and PFS was better for patients with high levels of HDL-C (≥ 1.19 mmol/L) compared to those with low levels of HDL-C (< 1.19 mmol/L) (P = 0.001).Conclusions: Preoperative HDL-C and LDL-C levels are significant predictors of clinical outcome in patients with epithelial ovarian cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Peng Li ◽  
Lei Wei ◽  
Wenshuai Zhu

Background. Osteosarcoma (OS) is the most frequent bone tumor with high metastasis. This study is aimed at assessing the expression and prognostic significance of microRNA-1826 (miR-1826) in OS patients, as well as its biological function in tumor progression. Methods. Quantitative Real-Time PCR was employed to measure the expression of miR-1826 in OS tissues and cell lines. Kaplan-Meier survival analysis and Cox regression model were used to evaluate the prognostic value of miR-1826. CCK-8 and Transwell assay were conducted to investigate the effect of miR-1826 on OS cell proliferation, migration, and invasion. Results. miR-1826 expression was downregulated in OS tissues and cell lines and associated with OS patients’ clinical stage and distant metastasis. Low levels of miR-1826 were related with shorter survival time and determined as an independent prognostic indicator for the overall survival of OS patients. The overexpression of miR-1826 in OS cells led to inhibited cell proliferation, migration, and invasion. Conclusion. The decreased expression of miR-1826 predicts a poor prognosis in OS patients, and its overexpression inhibits OS cell proliferation, migration, and invasion. This newly identified miR-1826 provides a novel sight into the pathogenesis of OS and offers a candidate prognostic biomarker and therapeutic target for OS treatment.


2003 ◽  
Vol 21 (16) ◽  
pp. 3119-3126 ◽  
Author(s):  
George M. Yousef ◽  
Andreas Scorilas ◽  
Dionyssios Katsaros ◽  
Stefano Fracchioli ◽  
Lisa Iskander ◽  
...  

Purpose: KLK15 is a newly cloned human kallikrein gene. Many kallikreins were found to be differentially expressed in ovarian cancer. Like other kallikreins, KLK15 is regulated by steroid hormones in cancer cell lines. KLK15 is upregulated mainly by androgens and to a lesser extent by progestins. The purpose of this study was to examine the prognostic value of KLK15 in ovarian cancer tissues.Materials and Methods: We studied KLK15 expression by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 168 consecutive patients with epithelial ovarian cancer. Ten patients with benign ovarian tumors were also included in the study. An optimal cutoff point equal to the 50th percentile was defined based on the ability of KLK15 to predict progression-free survival and overall survival of the study population.Results: KLK15 expression levels were significantly higher in cancerous tissues compared with benign tumors. Kaplan-Meier survival curves showed that KLK15 overexpression is a significant predictor of reduced progression-free survival (PFS; P < .001) and overall survival (OS; P < .009). Univariate and multivariate analyses indicate that KLK15 is an independent prognostic factor for PFS and OS. A weak positive correlation was found between KLK15 expression and serum CA-125 levels.Conclusion: KLK15 expression, as assessed by quantitative RT-PCR, is an independent marker of unfavorable prognosis for ovarian cancer.


Author(s):  
Toshihiko Shiraishi ◽  
Kei Suzuki ◽  
Shin Morishita ◽  
Hiroshi Kanno

In this study, sinusoidal inertia force was applied to cultured neural stem cells and the effects of mechanical vibration on the cells were investigated. Neural stem cells which were obtained from the hippocampus of an adult Fischer rat were seeded in culture plates at the density of 2.5 × 105 cells/ml. After cells were cultured for one day and adhered on the cultured plate, vibration groups of the culture plates were set on the aluminum plate of the experimental setup and cultured under sinusoidal excitation in another CO2 incubator separated from non-vibration groups of the culture plates. Acceleration amplitude was set to 0.25 or 0.5 G and frequency was set to 12.5, 25, or 50 Hz. Time evolution of cell density was obtained by counting the number of cells with a hemocytometer. The expression of Akt, phosphorylated Akt, MAPK, and phosphorylated MAPK was detected by western blotting analysis to understand the mechanism of cell proliferation. Gene expression of MAP-2, neurofilament-H, GFAP, and nestin was detected by a real-time RT-PCR method to obtain a ratio of differentiation of neural stem cells to nerve or glia cells. The results to be obtained are as follows. The mechanical vibration at 25 Hz is most effective on cell proliferation of the present experimental conditions at 0.25 G. The enhancement of cell proliferation is probably caused by the suppression of apoptosis. The differentiation of the neural stem cells depends on acceleration amplitude and the mechanical vibration may maintain some properties of stem cells.


2020 ◽  
Vol 20 (9) ◽  
pp. 689-699
Author(s):  
Xuemeng Lei ◽  
Xukun Li ◽  
Hongyan Chen ◽  
Zhihua Liu

Background: Ubiquitin specific protease 48 (USP48) is a member of the deubiquitinating enzymes (DUBs) family. However, the function of USP48 in ovarian cancer remains unclear. Objective: The present study reveals that USP48 knockdown could significantly inhibit cell migration and invasion in ES2, 3AO and A2780 cells, without affecting cell proliferation. Methods: After carboplatin (CBP) treatment, the USP48 ablation increases the apoptosis rate, and the cleaved PARP and cleaved caspase 3 expression levels in ES2, 3AO and A2780 cells. The subcutaneous tumor and intraperitoneally injected experiments demonstrated that the USP48 knockdown significantly increases responsiveness to CBP, and alleviates the metastasis in vivo. Meanwhile, USP48 deficiency results in the improved survival of mice. Results: Finally, the analysis of clinical samples and the TCGA and Kaplan-Meier Plot database revealed that the high expression of USP48 in ovarian cancer patients is associated with poor survival and resistance to CBP therapy. Conclusion: In summary, USP48 may be a potential therapeutic target for ovarian cancer patients.


2018 ◽  
Vol 18 (7) ◽  
pp. 1025-1031
Author(s):  
Cheng Luo ◽  
Di Wu ◽  
Meiling Chen ◽  
Wenhua Miao ◽  
Changfeng Xue ◽  
...  

Background: Different saponins from herbs have been used as tonic or functional foods, and for treatment of various diseases including cancers. Although clinical data has supported the function of these saponins, their underlying molecular mechanisms have not been well defined. Methods: With the simulated hypoxia created by 8 hours of Cu++ exposure and following 24 hour incubation with different concentration of saponins in HepG2 cells for MTT assay, migration and invasion assays, and for RT-PCR, and with each group of cells for immunofluorescence observation by confocal microscopy. Results: ZC-4 had the highest rate of inhibition of cell proliferation by MTT assay, and the highest inhibition of migration rate by in vitro scratch assay, while ZC-3 had the highest inhibition of invasion ratio by transwell assay. Under the same simulated hypoxia, the molecular mechanism of saponin function was conducted by measuring the gene expression of Hypoxia Inducible Factor (HIF)-1α through RT-PCR, in which ZC-3 showed a potent inhibition of gene HIF-1α. For the protein expression by immunofluorescence staining with confocal microscopy, HIF-1α was also inhibited by saponins, with the most potent one being ZC-4 after eight hours’ relatively hypoxia incubation. Conclusion: Saponins ZC-4 and ZC-3 have the potential to reduce HepG2 cell proliferation, migration and invasion caused by hypoxia through effectively inhibiting the gene and protein expression of HIF-1α directly and as antioxidant indirectly


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