BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer.

Bcl2-associated athanogene 3 (BAG3) has been reported to be elevated in various tumors. However, it is unclear whether BAG3 has a functional role in the initiation and progression of colorectal cancer (CRC). Here, we collected CRC samples and cell lines to validate the pathway by using gene and protein assays. RT-PCR showed that the expression of BAG3 mRNA in CRC tissues was obviously higher than that in non-tumor tissues (p < 0.001). Immunohistochemical analysis showed that immunoreactivity of BAG3 was found in most CRC tissues and strongly correlated with TNM stage (p = 0.001), differentiation (p = 0.003), and metastasis (p = 0.010). Low expression of BAG3 in HCT-8 significantly reduced cellular proliferation, migration, and invasion. The analysis of in vitro cell showed that HCT-8 cells were exposed to si-BAG3, and its growth was inhibited depending on modulation of cell cycle G1/S checkpoints and cell cycle regulators, involving cyclin D1, cyclin A2, and cyclin B1. Furthermore, suppression of the epithelial-mesenchymal transition (EMT) by si-BAG3 is linked to the decreased expression of E-cadherin and the increased expression of N-cadherin, vimentin, and MMP9. In conclusion, in the present study, we demonstrated that BAG3 overexpression plays a critical role in cell proliferation, migration, and invasion of colorectal cancer. Our data suggests targeted inhibition of BAG3 may be useful for patients with CRC.

MicroRNA­499 rs3746444 A/G polymorphism functions as a biomarker to predict recurrence following endoscopic submucosal dissection in primary early gastric cancer.

The aim of the present study was to investigate the molecular mechanism, including the potential regulatory and signaling pathways, of platelet­derived growth factor receptor ß (PDGFRB), which underlies the recurrence of early gastric cancer (EGC) following endoscopic submucosal dissection (ESD). Online microRNA (miRNA) target prediction tools were used, which identified PDGFRB as the candidate target gene of miR­499a in gastric cancer cells, and PFGRBR was then confirmed as the direct gene using a luciferase reporter assay system. The Kaplan­Meier method was used to plot recurrence­free curves, which were compared between genotype groups. A negative regulatory association between miR­499a and PDGFRB was established by investigating the relative luciferase activity at different concentrations of miR­499a mimics. Furthermore, as the rs3746444 polymorphism has been previously reported to interfere with the expression of miR­499a, the present study investigated the expression levels of different genotypes, including TT (n=20), TC (n=9) and CC (n=3), the results of which supported the hypothesis that the presence of the minor allele (C) of the rs3746444 polymorphism compromised the expression of miR­499a. The present study also performed polymerase chain reaction and western blot analyses to examine the mRNA and protein expression levels of PFGRBR among different genotypes or cells treated with different concentrations of miR­499a mimics/inhibitors, which indicated the negative regulatory association between miR­499a and PDGFRB. The present study also investigated the relative viabilities of EGC cells transfected with miR­499a mimics (50 and 100 nM) and miR­499a inhibitors (100 nM), and confirmed that miR­499a negatively interfered with the viability of the EGC cells. The miR­499a rs3746444 polymorphism was also recognized as a biomarker to predict recurrence following ESD in patients with EGC via analyzing the recurrence­free rates among patients with EGC with different genotypes. The results showed that PDGFRB was validated as a target of miR­499a, and rs3746444 was identified as a potential biomarker to predict the recurrence of EGC following ESD.

[Efficacy meta-analysis of laparoscope-assisted transanal total mesorectal excision and conventional laparoscopic excision for rectal cancer].

OBJECTIVE: To compare the short-term efficacy of laparoscope-assisted transanal total mesorectal excision (LA-taTME) and conventional laparoscopic TME (LTME) for rectal cancer by meta-analysis. METHODS: Clinical studies that compared clinical outcomes of LA-taTME and LTME were searched from form PubMed, Embase, Ovid, CNKI and Wanfang database before January 2016. Two reviewers independently screened the articles and assessed the quality of the included studies by using the MINORS standard which involves 12 items. The score is 0-2 for each item and the maximum score is 24, and the ideal global score should be above16. RevMan 5.3 software was used for meta-analysis and outcome measures included operation time, hospital stay, number of harvested lymph node, rate of conversion, positive rate of circumferential resection margin and the rate of incomplete mesorectum. RESULTS: Seven studies were included in the analysis, and the score of all the studies was more than 16 points. A total of 479 patients (208 in LA-taTME, 271 in LTME) were enrolled. There were no significant differences in terms of age, sex, tumor location and clinical stage between two groups (all P>0.05). Results of meta-analysis showed that LA-taTME had lower rate of incomplete mesorectum (OR=0.29, 95% CI:0.10 to 0.84, P=0.02), lower rate of complications (OR=0.59, 95% CI:0.35 to 0.97, P=0.04) and shorter hospital stay (MD=-1.66, 95% CI:-3.22 to -0.11, P=0.04) than those of LTME, with significant differences. In terms of operation time (MD=-14.49, 95% CI:-37.87 to 8.90, P=0.22), number of harvested lymph node (MD=-0.45, 95% CI:-1.98 to 1.08, P=0.56), the rate of conversion (OR=0.31, 95% CI:0.08 to 1.24, P=0.10) and positive rate of circumferential resection margin (OR=0.43, 95% CI:0.17 to 1.04, P=0.06), there were no significant differences between two groups. CONCLUSION: Compared to LTME, LA-taTME has similar short-term efficacy for rectal cancer, but it can reduce the rate of complications and rate of incomplete mesorectum.

A novel spherical magnetic compression device for colorectal anastomosis in a Swine model.

BACKGROUND: We designed a novel, spherical magnetic compression colorectal anastomosis device and established a swine model to assess the feasibility and safety, as well as advantages, of the device. METHODS AND MATERIALS: Fifteen animals were divided into five groups (sacrificed on Days 3, 5 7, 9, and 14) with 3 in each group. In each group, a magnetic compression device was used in 2 animals (experimental animals), and a stapled device was used in 1 animal (control animal). Feeding status, bowel movements, the discharge time of the magnetic anastomosis device, burst pressure, and magnetic field strength were recorded. Gross anatomical and histological examinations were performed. RESULTS: The average device discharge time was 7.5 days. The burst pressure increased over time for both the experimental and control animals. Both the gross anatomical and histological examinations suggested that the inflammatory reaction was milder. Healing occurred more quickly, and the incidence of complications was lower for the experimental animals than for the control animals. CONCLUSIONS: The potential benefits of the spherical magnetic compression colorectal anastomosis device, relative to the stapled device, were in terms of effectiveness and complication incidence, which encourages us to further study its application in gastrointestinal anastomosis.