Ovarian cancer is one of the leading causes of death from gynecological malignancies. Despite the improvement in surgical techniques and the advent of more effective therapeutics, the overall 5-year survival has increased only from 36% to 44% during the past three decades (Siegel et al. 2012). More than 80% of ovarian cancers are of epithelial origin, which are highly invasive, respond poorly to therapies, and are usually detected at advanced stages, resulting in poor prognosis (Auersperg et al. 2002;Jordan et al. 2006). To improve better prognostic and predictive assays and develop new therapeutic strategies for epithelial ovarian cancer (EOC), we must understand the molecular mechanisms underlying EOC.Arginine methylation is becoming more acknowledged as an important type of posttranslational modification found in both nuclear and cytoplasmic proteins (Bedford and Richard 2005;Bedford and Clarke 2009). The posttranslational modification of protein arginine methylation is widely appreciated, playing a vital role in cellular function. The methylation of arginine residues is catalyzed by the protein arginine methyltransferases (PRMTs), which can catalyze the addition of one or two methyl groups to the guanidine nitrogen atoms of arginine. To date, PRMT family have been found 11 members in humans (including PRMT1-11), and most PRMTs, with the exception of PRMT2, PRMT10, and PRMT11, have been shown to have enzymatic activity and can catalyze arginine methylation (Bedford and Richard 2005;. Based on the primary protein sequence and the specificity for distinct substrates, PRMTs are mainly classified as type I and type II enzymes. These two types of enzymes catalyze the formation of a Summary PRMT5 has been reported to be involved in the processes of tumor progression at various steps. The aim of this study was to examine the role of PRMT5 in epithelial ovarian cancer (EOC). In this study, PRMT5 and Ki-67 expression were examined by immunohistochemistry (IHC) in cohorts of normal, benign, and cancerous ovarian tissues. PRMT5 overexpression was observed in 83.1% (98/118) of EOCs, and it was significantly associated with serous type, poor differentiation, advanced tumor stage, lymph node invasion, presence of residual tumor, and high expression of respectively). Moreover, overexpression of PRMT5 was an independent prognostic marker for decreased overall survival and progression-free survival in univariate survival analysis and multivariate Cox regression analysis. In ovarian cancer cell lines A2780 and SKOV3, PRMT5 knockdown by siRNA inhibited cell growth/proliferation and induced apoptosis via upregulation of E2F-1. These results suggest that overexpression of PRMT5 correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for EOC. Thus, PRMT5 may represent a clinically effective new target for therapy of ovarian cancer. (J Histochem Cytochem 61:206-217, 2013) 475452J HCXXX10.1369/0022155413475452B ao et al.PRMT5 in Epithelial Ovarian Cancer 2013© The Author(s) 2010 Reprints and...
The transport protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1. In mammals, structures and functions of various TRAPP complexes are beginning to be understood. We found that mammalian TRAPPII was a GEF for both Rab18 and Rab1. Inactivation of TRAPPII-specific subunits by various methods including siRNA depletion and CRISPR-Cas9-mediated deletion reduced lipolysis and resulted in aberrantly large lipid droplets. Recruitment of Rab18 onto lipid droplet (LD) surface was defective in TRAPPII-deleted cells, but the localization of Rab1 on Golgi was not affected. COPI regulates LD homeostasis. We found that the previously documented interaction between TRAPPII and COPI was also required for the recruitment of Rab18 to the LD. We hypothesize that the interaction between COPI and TRAPPII helps bring TRAPPII onto LD surface, and TRAPPII, in turn, activates Rab18 and recruits it on the LD surface to facilitate its functions in LD homeostasis.
Preventing anastomotic leakage (AL) is crucial for colorectal surgery. Some studies have suggested a positive role of transanal drainage tubes (TDTs) in AL prevention after low anterior resection, but this finding is controversial.OBJECTIVE To assess the effect of TDTs in AL prevention after laparoscopic low anterior resection for rectal cancer. DESIGN, SETTING, AND PARTICIPANTSThis multicenter randomized clinical trial with parallel groups (TDT vs non-TDT) was performed from February 26, 2016, to September 30, 2020. Participants included patients from 7 different hospitals in China who were undergoing laparoscopic low anterior resection with the double-stapling technique for mid-low rectal cancer; 576 patients were initially enrolled in this study, and 16 were later excluded. Ultimately, 560 patients were randomly divided between the TDT and non-TDT groups.INTERVENTIONS A silicone tube was inserted through the anus, and the tip of the tube was placed approximately 5 cm above the anastomosis under laparoscopy at the conclusion of surgery. The tube was fixed with a skin suture and connected to a drainage bag. The TDT was scheduled for removal 3 to 7 days after surgery. MAIN OUTCOMES AND MEASURESThe primary end point was the postoperative AL rate within 30 days. RESULTSIn total, 576 patients were initially enrolled in this study; 16 of these patients were excluded. Ultimately, 560 patients were randomly divided between the TDT group (n = 280; median age, 61.5 years [IQR, 54.0-68.8 years]; 177 men [63.2%]) and the non-TDT group (n = 280; median age, 62.0 years [IQR, 52.0-69.0 years]; 169 men [60.4%]). Intention-to-treat analysis showed no significant difference between the TDT and non-TDT groups in AL rates (18 [6.4%] vs 19 [6.8%]; relative risk, 0.947; 95% CI, 0.508-1.766; P = .87) or AL grades (grade B, 14 [5.0%] and grade C, 4 [1.4%] vs grade B, 11 [3.9%] and grade C, 8 [2.9%]; P = .43). In the stratified analysis based on diverting stomas, there was no significant difference in the AL rate between the groups, regardless of whether a diverting stoma was present (without stoma, 12 [5.8%] vs 15 [7.9%], P = .41; and with stoma, 6 [8.3%] vs 4 [4.5%], P = .50). Anal pain was the most common complaint from patients in the TDT group (130 of 280, 46.4%). Accidental early TDT removal occurred in 20 patients (7.1%), and no bleeding or iatrogenic colonic perforations were detected. CONCLUSIONS AND RELEVANCEThe results from this randomized clinical trial indicated that TDTs may not confer any benefit for AL prevention in patients who undergo laparoscopic low anterior resection for mid-low rectal cancer without preoperative radiotherapy.
Backgrounds/Aims: MicroRNAs (MiRNAs) control many biological events and play critical roles in the development of tumor. Among all miRNAs, miR203 has been recently shown to have an inhibitory effect on prostate cancer. However, its involvement in the carcinogenesis of breast cancer has not been reported. Methods: We examined the levels of miR203 in the breast cancer from the patients compared to the paired normal breast tissue. We also examined the levels of miR203 in several commonly used breast cancer cell lines. The effects of overexpression or depletion of miR203 on breast cancer cell growth were analyzed by a MTT assay, and on breast cancer cell invasion were examined by a scratch wound healing assay and a transwell cell migration assay. MiR203-targeted genes were analyzed by Western blot. Results: We detected significantly lower levels of miR203 in the breast cancer from the patients compared to the paired normal breast tissue. Moreover, the levels of miR203 were significantly lower in breast cancer tissue from the patients with cancer metastasis. Decreased miR203 levels were detected in all examined breast cancer lines. Overexpression of miR203 inhibited breast cancer cell growth and invasion, while antisense-mediated inhibition of miR203 enhanced cancer cell growth and invasion. Further analyses show that miR203 may inhibit cell growth through decreasing cell-cycle activator cyclinD2 and CDK6, increasing cell-cycle suppressor p21 and p27, and increasing apoptosis-associated protein Bcl-2. MiR203 may also inhibit cell metastasis through suppressing matrix metalloproteinase 2 (MMP2), MMP7 and MMP9. Conclusion: Our data thus highlight miR203 as a novel therapeutic target for breast cancer.
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