Accumulating evidence shows that microRNAs, functioning as either oncogenes or tumour suppressors by negatively regulating downstream target genes that are actively involved in tumour initiation and progression, may be promising biomarkers and therapy targets. Data mining through a microRNA chip database indicated that let-7c may be associated with tumour metastasis. Here, we confirmed that down-regulation of let-7c in primary cancer tissues was significantly associated with metastases, advanced TNM stages and poor survival of colorectal cancer patients. Moreover, ectopic expression of let-7c in a highly metastatic Lovo cell line remarkably suppressed cell migration and invasion in vitro by the down-regulation of K-RAS, MMP11 and PBX3, as well as tumour growth and metastases in vivo, whereas inhibition of let-7c in low-metastatic HT29 cells increased cell motility and invasion by the enhanced gene expression of K-RAS, MMP11 and PBX3. Interestingly, the luciferase reporters' activities with the 3'-UTRs of K-RAS, MMP11 and PBX3 were inhibited significantly by let-7c. Importantly, rescue experiments involving the over-expression of these genes without their 3'-UTRs completely reversed the effects of let-7c on tumour metastasis, both in vitro and in vivo. Finally, the levels of let-7c were inversely correlated with those of MMP11 and PBX3, but not with those of K-RAS. Taken together, these results demonstrate that let-7c, apart from its tumour growth suppression role, also functions as a tumour metastasis suppressor in colorectal cancer by directly destabilizing the mRNAs of MMP11 and PBX3 at least.

Hepatocellular carcinoma (HCC) is associated with a high morbidity and mortality due to its high rate of recurrence. However, little is known about the biological characteristics of recurrent HCC cells. A single patient's primary and recurrent HCC-derived cell lines, Hep-11 and Hep-12, respectively, were established by primary culture. These two cell lines have the same hepatitis B virus integration site and share many common amplifications and deletions, which suggest that they have the same clonal origin. While Hep-11 cells were non-tumorigenic at 16 weeks following injection of up to 10 000 cells, injection of only 100 Hep-12 cells was sufficient to initiate tumor growth, and all single Hep-12 clones were tumorigenic in immunodeficient mice. Compared with Hep-11, Hep-12 cells expressed the oval cell markers AFP, NCAM/CD56, c-kit/CD117, as well as multiple stem cell markers such as Nanog, OCT4 and SOX2. In addition, >90% of Hep-12 cells were aldehyde dehydrogenase positive. They were also less resistant to paclitaxel, but more resistant to doxorubicin, cisplatin and hydroxycamptothecin (HCPT), which had been administrated to the patient. Furthermore, Hep-12 cells expressed higher levels of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) than Hep-11, and PARP-1 inhibition potentiated the sensitivity to HCPT in Hep-12 cells but not in Hep-11 cells. These results indicate that a large population of the recurrent HCC-derived Hep-12 cells were tumor-initiating cells and that elevated expression of PARP-1 was related to their resistance to HCPT.

PBX3 induces invasion and metastasis of CRC cells partially through activation of the MAPK/ERK signaling pathway.

No abstract

We explore the effects of hydrogenated annealing on the crystal structure, room temperature ferromagnetism (RT-FM) and photoluminescence (PL) properties of Ni-doped ZnO (Zn1−xNixO, x=0.0 to 0.2) nanoparticles prepared by a sol-gel method. The x-ray photoelectron spectra and x-ray diffraction data provide evidence that Ni has been incorporated into the wurtzite ZnO lattice as Ni2+ ions substituting for Zn2+ ions at x≤0.05. A secondary phase of NiO type begins to form inside ZnO when x>0.05 and segregates from ZnO host lattice at x=0.2, leading to a large variation in the lattice constants of ZnO. The magnetization measurements show that the saturation magnetization (Ms) increases with increasing Ni concentration in the single-phase Zn1−xNixO (x≤0.05) nanoparticles. The secondary phase formation reduces the magnetization of Zn1−xNixO (x=0.1 and 0.15), while the segregation of NiO from the ZnO lattice at x=0.2 is accompanied by a large increase in Ms again. The PL measurements show that the UV emission intensity of single-phase Zn1−xNixO (x≤0.05) nanoparticles increases with a blueshift in the UV emission line when the Ni concentration increases, while the dominant green emission intensity decreases with increasing Ni dopant. The PL data strongly suggest that the FM in single-phase Zn1−xNixO (x≤0.05) nanoparticles is intrinsically correlated with a doping induced increase in the electron concentration in the conduction band of Ni-doped ZnO. After H2-annealing, the single-phase Zn1−xNixO:H (x≤0.05) nanoparticles show increases in both coercivity and saturation magnetization. The PL and diffuse reflectance spectra suggest that hydrogen-related shallow donors and an improved sample quality may be responsible for the H2-annealing induced enhancement of the RT-FM. The obvious correlation between FM and carrier concentration in Ni and Ni–H doped ZnO points towards a mechanism of carrier-mediated FM for Ni-doped ZnO diluted magnetic semiconductors.