[Retracted] MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration data shown in Figs. 2D and 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 38: 1587­1595, 2016; DOI: 10.3892/ijmm.2016.2754].

THBS2 is a biomarker for AJCC stages and a strong prognostic indicator in colorectal cancer.

PURPOSE: To investigate the expression of thrombospondin 2 (THBS2) in colorectal cancer (CRC) and its relationship with clinicopathological features and prognosis. METHODS: THBS2 expression was evaluated with tissue microarrays (TMAs) immunohistochemistry (IHC) staining in 100 CRC samples. RESULTS: High THBS2 expression was found in 73 patients (45 male and 28 female). THBS2 expression was significantly correlated to TNM stages (p=4.1×10-5), T classification (p=0.005), lymph node metastasis (p=3×10-4) and AJCC stages (p=0), while no significant association was found in gender, age, distant metastasis or tumor size. In both univariate and multivariate analyses, THBS2 showed statistically prognostic significance [p<0.001, HR (hazard ratio) = 0.237, 95% CI (0.101-0.557) and p<0.001, HR=0.158, 95% CI (0.062-0.401)]. Kaplan-Meier survival analysis further confirmed that THBS2 expression was significantly correlated with clinical outcomes (p<0.001). CONCLUSIONS: All the results indicated THBS2 expression might become a prognostic marker for CRC.

IGFBP7 is associated to prognosis and could suppress cell survival in cholangiocarcinoma.

Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein and its expression was restrained in varied solid tumours, but there was no report about biological role of IGFBP7 in cholangiocarcinoma (CCA). Here, we found that high expression of IGFBP7 correlated to a better overall survival in CCA patients. To investigate the hypothetic antineoplastic activity of IGFBP7 in CCA, we induced overexpression of IGFBP7 in QBC939 and RBE cells, as well as knockdown in HCCC9810 cells. And the biological functions triggered by level changes of IGFBP7 were assessed, including proliferation, cell cycle distribution, apoptosis and invasion evaluation. Cell growth assessment showed that enhanced IGFBP7 expression significantly retarded proliferation rates of QBC939 and RBE cells while an enhancement was observed in IGFBP7-inhibited HCCC9810 cells. The inhibition of cell viability was induced via G2/M phase arrest and apoptosis. Both QBC939 and RBE cells possess highly invasive ability, and IGFBP7 overexpression attenuated their serious invasiveness by reversing their mesenchymal phenotype to endothelial signature. We next investigated the potential mechanism involving in IGFBP7-induced tumour suppression and found that increased expression of IGFBP7 resulted in decrease of IGF-IR, IRS-1 and phosphor-AKT protein levels, accompanied with elevation of phorsphor-p38MAPK. These results suggest that IGFBP7 might be related to CCA carcinogenesis and metastasis, which further implicates that IGFBP7 might become a prospective benchmark for CCA diagnosis and therapy.

MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression.

MicroRNAs (miRNAs or miRs) have been found to participate in the development and malignant progression of human cancers by negatively mediating the expression of their target genes. Recently, miR­33b has been reported to be involved in multiple types of human cancer, including hepatocellular carcinoma (HCC). However, the underlying regulatory mechanisms of miR­33b in HCC cell growth and metastasis remain largely unclear. In the present study, RT-qPCR revealed that miR­33b was significantly downregulated in HCC tissues compared to their matched adjacent normal tissues. Moreover, the miR­33b level was significantly lower in advanced-stage HCC (stages T3-T4) compared to early-stage HCC (stages T1-T2). Furthermore, it was also downregulated in the HCC cell lines, LH86, HepG2, LMH and PLHC-1, when compared with the THLE-3 normal human liver cells. We further demonstrated that the overexpression of miR­33b led to a significant decrease in the proliferation, migration and invasion of HepG2 and LH86 cells. Luciferase reporter assay identified Sal-like protein 4 (SALL4) as a target gene of miR­33b, and its protein expression was negatively regulated by miR­33b in HepG2 and LH86 cells. Moreover, the restoration of SALL4 expression markedly reversed the inhibitory effect of miR­33b overexpression on the proliferation, migration and invasion of HepG2 and LH86 cells, indicating that SALL4 is involved in miR­33b-mediated malignant phenotypes of HCC cells. Furthermore, we found that SALL4 was significantly upregulated in HCC tissues compared to their matched adjacent normal tissues, and its increased expression was significantly associated with the advanced malignancy of HCC. Moreover, SALL4 was also upregulated in HCC cell lines compared to the THLE-3 normal human liver cells. Finally, we found that the SALL4 expression inversely correlated with the miR­33b level in HCC tissues. On the whole, the findings of our study demonstrate that miR­33b suppresses the proliferation and metastasis of HCC cells through the inhibition of SALL4 expression. Therefore, miR­33b/SALL4 may become a potential therapeutic target for the treatment of HCC.

MiR-503 inhibits hepatocellular carcinoma cell growth via inhibition of insulin-like growth factor 1 receptor.

MicroRNAs (miRs) have been demonstrated to play key roles in the development and progression of hepatocellular carcinoma (HCC). However, the regulatory mechanism of miR-503 in HCC has not been fully uncovered. In this study, we found that miR-503 was significantly downregulated in HCC tissues compared to nontumorous liver tissues. Moreover, lower miR-503 levels were associated with the malignant progression of HCC, and the expression of miR-503 was also decreased in several common HCC cell lines compared to normal human liver cell line THLE-3. Overexpression of miR-503 inhibited proliferation but induced apoptosis of LM3 and HepG2 cells. Bioinformatical analysis and luciferase reporter assay further identified insulin-like growth factor 1 receptor (IGF-1R) as a novel target of miR-503 in 293T cells. Moreover, overexpression of miR-503 led to a significant decrease in the protein levels of IGF-1R, while knockdown of miR-503 enhanced its protein levels in LM3 and HepG2 cells. Besides, overexpression of IGF-1R reversed the effects of miR-503-mediated HCC cell proliferation and apoptosis, indicating that IGF-1R acts as a downstream effector of miR-503 in HCC cells. Furthermore, IGF-1R was found to be significantly upregulated in HCC tissues compared to nontumorous liver tissues. In addition, the mRNA levels of IGF-1R were inversely correlated to the miR-503 levels in the HCC tissues. Thus, we demonstrate that miR-503 inhibits the proliferation and induces the apoptosis of HCC cells, partly at least, by directly targeting IGF-1R, and suggest that IGF-1R may serve as a promising target for the treatment of HCC.

[Risk factors of cholecystitis after radical gastrectomy for gastric cancer].

OBJECTIVE: To investigate the risk factor of cholecystitis after radical gastrectomy for gastric cancer. METHODS: Clinicpathological data of 553 gastric cancer patients with normal gallbladders undergoing radical gastrectomy in Tianjin Medical University Cancer Institute and Hospital between March 2013 and March 2015 were analyzed retrospectively. Univariate and multivariate analysis were applied to evaluate factors influencing the cholecystitis after radical gastrectomy using log-rank and logistic regression model. RESULTS: There were 360 males and 193 females with a median age of 60 years. All patients were followed up from 6 months to 2 years. The incidence of cholecystitis after radical gastrectomy for gastric cancer was 33.1%(183/553), while incidence of cholecystolithiasis was 4.9%(27/553). In addition, the cholecystitis incidence of patients with No.12 lymph node cleaning was 39.6%(89/225), while with No.8a lymph node cleaning was 38.0%(151/397), with No.5 lymph node cleaning was 38.0%(68/179), with No.7 lymph node cleaning was 34.4%(138/402), with No.9 lymph node cleaning was 34.7%(136/392). Univariate log-rank test indicated that the lymphadenectomy of No.8a(χ(2)=15.530, P=0.000), No.12 group(χ(2)=7.157, P=0.007) and surgical methods (χ(2)=7.427, P=0.024) were significantly associated with cholecystitis after radical gastrectomy. Multivariate analysis showed that the lymphadenectomy of No.8a was independent factor of cholecystitis after radical gastrectomy (OR=2.016, 95% CI:1.244 to 3.267, P=0.004). CONCLUSIONS: Vagal nerve trunk and sympathetic ganglion should be protected carefully during No.8a lymphadenectomy in radical gastrectomy for gastric cancer, in order to reduce the incidence of postoperative cholecystitis.