BackgroundRecently, miR-10b is identified as a miRNA highly expressed in many human cancers, promoting cell migration and invasion. However, the specific function of miR-10b in hepatocellular carcinoma (HCC) is unclear at this point.MethodsThe miR-10b expression levels in 60 paired different TNM Stage HCC tumor tissues compared with adjacent non-tumor (ANT) tissues, normal tissue control (8 benign tumor and 7 normal liver tissues), 3 normal liver and 7 HCC cell lines were measured by real-time quantitative RT-PCR and to evaluate their association with HCC clinicopathologic features. Invasion assay, MTT proliferation assay and wound-healing assay were performed to test the invasion and proliferation of HCC cell after transfection. The effect of miR-10b on HCC in vivo was validated by murine xenograft model.ResultsWe found that miR-10b expression was increased in human HCC tissues and cell lines compared with normal control, respectively. The expression of miR-10b was correlated with HCC metastatic ability. Overexpression of miR-10b in MHCC-97L cells increased cell motility and invasiveness, whereas inhibition of miR-10b in MHCC-97H cells reduced cell motility and invasiveness in vitro and in vivo. We also showed that HOXD10 was negatively regulated by miR-10b at the posttranscriptional level, via a specific target site within the 3′UTR by luciferase reporter assay. Furthermore, we found that miR-10b induced HCC cell invasion and migration by modulating the HOXD10 target gene RhoC, uPAR, MMP-2 and MMP-9 expression.ConclusionsOur results suggested that miR-10b was overexpressed in HCC and promoted HCC cell migration and invasion through the HOXD10/ RhoC/ uPAR/ MMPs pathway which may provide a novel bio-target for HCC therapy.

Xeroderma pigmentosum complementation group C and G (XPC, XPG) play important roles in DNA damage repairing machinery. Genetic variations in the XPC and XPG may be associated with increased risk for colorectal carcinoma (CRC). In this study, we evaluated the relation between the XPC Lys939Gln, XPG Asp1104His polymorphisms, and CRC susceptibility in a population-based case-control study, which included 1,028 CRC cases and 1,085 controls. Compared with the corresponding wild genotypes, we found that individuals with at least one copy of the XPC Lys939Gln (AC or CC genotype) and XPG Asp1104His (GC or CC genotype) had an increased risk for CRC. In addition, the variant genotypes of the XPC Lys939Gln AC/CC (P = 0.027) or XPG Asp1104His GC/CC (P = 0.003) reduced the elevation of preoperative carcinoembryonic antigen (CEA) level. Moreover a significantly longer progression-free survival (PFS) after Oxaliplatin-based adjuvant chemotherapy was observed in patients with XPG Asp1104His wide-type GG genotype (n = 432, Log-rank test: P = 0.033). Cox proportional hazards analyses demonstrated that variant genotypes of XPG Asp1104His [hazard ratio (HR) = 1.692, 95% confidence interval (95%CI): 1.202-2.383, P = 0.003] as well as pathology grade (HR = 2.545, 95%CI: 2.139-3.030, P < 0.001), and lymph node metastases (HR = 1.851, 95%CI: 1.306-2.625, P < 0.001) were predictive of shorter PFS for the CRC patients with Oxaliplatin-based adjuvant chemotherapy. In conclusion, the current data suggested that XPC Lys939Gln and XPG Asp1104His polymorphisms might contribute to the identification of patients with increased risk for CRC.

These results suggest that ABCB1 gene C3435T, G2677T/A variations and haplotype 3435T-1236T-2677T relate to the risk and clinical outcomes of breast carcinoma and may function as candidate molecular markers of anthracycline chemosensitivity in breast carcinoma.

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SFN improves abnormal lipid metabolism via both ER-stress-dependent and -independent pathways.

The complexity of tumor biology necessitates a multimodality approach that targets different aspects of tumor environment in order to generate the greatest benefit. IFN-inducible T cell alpha chemoattractant (ITAC)/CXCL11 and IFN-inducible protein 10 (IP10)/CXCL10 could exert antitumor effects with functional specificity and thus emerge as attractive candidates for combinatorial strategy. Disappointedly, a synergistic antitumor effect could not be observed when CXCL10 and CXCL11 were pooled together. In this regard, we seek to improve antitumor efficacy by integrating their individual functional moieties into a chemokine chimeric molecule, designated ITIP, which was engineered by substituting the N-terminal and N-loop region of CXCL10 with those of CXCL11. The functional properties of ITIP were determined by chemotaxis and angiogenesis assays. The antitumor efficacy was tested in murine CT26 colon carcinoma, 4T1 mammary carcinoma and 3LL lung carcinoma. Here we showed that ITIP not only exhibited respective functional superiority but strikingly promoted regression of established tumors and remarkably prolonged survival of mice compared with its parent chemokines, either alone or in combination. The chemokine chimera induced an augmented anti-tumor immunity and a marked decrease in tumor vasculature. Antibody neutralization studies indicated that CXCL10 and CXCL11 moieties of ITIP were responsible for anti-angiogenesis and chemotaxis in antitumor response, respectively. These results indicated that integrating individual functional moieties of CXCL10 and CXCL11 into a chimeric chemokine could lead to a synergistic antitumor effect. Thus, this integration strategy holds promise for chemokine-based multiple targeted therapy of cancer.

SUMMARYIcaritin, a hydrolytic product of icariin from the Epimedium genus, exerts anti-tumour effects on a variety of tumour cell types, mainly by inhibiting cell proliferation and inducing apoptosis. However, little is known about the role of icaritin in cancer invasion and epithelial-to-mesenchymal transition (EMT). In the present study, the glioblastoma (GBM) cell line U87MG was used as a model to investigate the effects of icaritin on the invasion and EMT of cancer cells. The results showed that icaritin significantly inhibited the invasion and EMT of GBM cells by targeting extracellular matrix metalloproteinase (EMMPRIN). Furthermore, the findings strongly indicate that the modulatory effect of icaritin on EMMPRIN is mediated via the PTEN/Akt/HIF-1a signalling pathway. The data provide the first experimental evidence of the inhibitory effect of icaritin on cancer cell invasion and EMT, thus highlighting the potential of icaritin to be employed as a promising anti-cancer agent in the treatment of GBM.