RESUMO
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. Minichromosome maintenance proteins (MCMs), particularly MCM2-7, are upregulated in various cancers, including HCC. The aim of the present study was to investigate the role of MCM2-7 in human liver HCC (LIHC) and the regulation of the protein homeostasis of MCM6 by a specific E3 ligase. Bioinformatics analyses demonstrated that MCM2-7 were highly expressed in LIHC compared with corresponding normal tissues at the mRNA and protein levels, and patients with LIHC and high mRNA expression levels of MCM2, MCM3, MCM6 and MCM7 had poor overall survival rates. Cell Counting Kit-8 and colony formation assays revealed that the knockdown of MCM2, MCM3, MCM6 or MCM7 in Huh7 and Hep3B HCC cells inhibited cell proliferation and colony formation. In addition, pull-down, co-immunoprecipitation and ubiquitination assays demonstrated that RNF125 interacts with MCM6 and mediates its ubiquitination. Furthermore, co-transfection experiments indicated that RNF125 promoted the proliferation of HCC cells mainly through MCM6. In summary, the present study suggests that the RNF125-MCM6 axis plays an important role in the regulation of HCC cell proliferation and is a promising therapeutic target for the treatment of LIHC.
RESUMO
OBJECTIVE: To explore the related factors of anastomotic leakfollowing anterior resection for the rectal cancer and the association of the preoperative nutritional risk screening 2002(NRS2002) score. METHODS: Clinical data of 396 rectal cancer patients who underwent elective anterior resection from January 2010 to July 2015 at Affiliated Lu'an Hospital of Anhui Medical University were collected. Patient's nutritional risk score on admission was calculated by NRS2002 scoring system according to original medical records. NRS2002 score less than 3 was defined as nutritious risk. Chi-squared test, or Fisher exact test and multivariate logistic regression wereused to analyze the association of the clinical pathological factors and NRS2002 risk factor with anastomotic leak. RESULTS: Of the 396 patients, NRS2002 score≥3, and anastomotic leak occurred in 157(39.6%) and 13(3.3%), respectively. In univariate analysis, different ages, NRS2002 score, preoperative intestinal obstruction, distance from anastomosis to anal vergeand tumor TNM stage were significantly associated with postoperative anastomotic leak(all P<0.05). The incidence of postoperative anastomotic leak among patients with NRS2002 score≥3 was significantly higher than those with NRS2002 score<3[6.4%(10/157) vs. 1.3%(3/239), χ(2)=7.806, P=0.005]. Multivariate analysis showed that NRS2002 score≥3(OR=3.988, 95% CI:1.004-15.837, P=0.049), existence of preoperative intestinal obstruction(OR=5.780, 95% CI:1.320 ~ 25.311, P=0.020),distance from anastomosis to anal verge≤5 cm(OR=0.236, 95% CI: 0.071 ~ 0.785, P=0.019) were the independent risk factors of anastomotic leak following anterior resection for the rectal cancer. CONCLUSION: Rectal cancer patients undergoing anterior resection with preoperative NRS2002 score≥3 should receive reasonable perioperative nutritional support to prevent anastomotic leak.