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Background: Distant metastasis is the major cause of cancer-related death, and epithelial-to-mesenchymal transition (EMT) has a critical role in this process. Accumulating evidence indicates that EMT can be regulated by microRNAs (miRNAs). miR-29c has been implicated as a tumor suppressor in several human cancers. However, the role of miR-29c in the progression of colorectal cancer (CRC) metastasis remains largely unknown., Patients and Methods: The expression of miR-29c was examined by qRT-PCR in a cohort of primary CRC (PC) and distant liver metastasis (LM) tissues. A series of in vivo and in vitro assays were carried out in order to elucidate the functions of miR-29c and the molecular mechanisms underlying the pathogenesis of metastatic CRC., Results: miR-29c was markedly downregulated in PCs with distant metastasis and determined to be an independent predictor of shortened patient survival. But LM tissues showed higher levels of miR-29c than that in PC tissues. In CRC cells, miR-29c dramatically suppressed cell migration and invasion abilities in vitro and cancer metastasis in vivo. In addition, miR-29c inhibited EMT and negatively regulated Wnt/β-catenin signaling pathway. Guanine nucleotide binding protein alpha13 (GNA13) and protein tyrosine phosphatase type IVA (PTP4A) were identified as direct targets of miR-29c, which acted through ERK/GSK3β/β-catenin and AKT/GSK3β/β-catenin pathways, respectively, to regulate EMT. Furthermore, significant associations between miR-29c, its target genes (GNA13 and PTP4A) and EMT markers were validated in both PC and LM tissues., Conclusion: Our findings highlight the important role of miR-29c in regulating CRC EMT via GSK-3β/β-catenin signaling by targeting GNA13 and PTP4A and provide new insights into the metastatic basis of CRC., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The amplified in breast cancer 1 (AIB1) gene has been considered to play an oncogenic role in human cancers, but its clinical/prognostic significance in non-small-cell lung cancer (NSCLC) is still unclear., Patients and Methods: The methods of immunohistochemistry and FISH were utilized to examine protein expression and amplification of AIB1 in 230 informative surgically resected NSCLCs and in 30 samples of normal lung tissues., Results: Overexpression and amplification of AIB1 were found in 48.3% and 8.2% of NSCLCs, respectively. AIB1 overexpression was associated with AIB1 gene amplification and cell proliferation but not related to estrogen receptor (ER)-alpha, ER-beta, progesterone receptor or androgen receptor status. A positive correlation between AIB1 overexpression and an ascending pathologic node stage in lung adenocarcinoma (ADC) was observed (P = 0.043). Univariate survival analysis demonstrated a significant association of AIB1 overexpression with shortened patient survival, especially for those with stage III disease (P < 0.001). Importantly, AIB1 expression was evaluated as the most significant predictor for survival in multivariate analysis (hazards ratio = 2.069, P < 0.001)., Conclusion: Overexpression of AIB1 might provide a selective advantage for lymph node metastasis of lung ADC and serve as a useful biomarker for poor prognosis for NSCLC patients.

Background/aims: To conduct a genome-wide analysis of loss of heterozygosity (LOH) and its clinical significance in hepatocellular carcinoma (HCC) in Southern China where high incidence of HCC was documented., Methods: LOH of 382 microsatellite loci on all autosomes were detected with polymerase chain reaction-based microsatellite polymorphism analyses in 104 HCC tumor tissues., Results: High frequency of LOH (>55.7%) was observed on chromosome 1p, 1q, 2q, 3p, 4q, 6q, 8p, 9p, 13q, 16q, and 17p. LOH rates on loci D4S2964 (4q21.21), D8S277 (8p23.1-pter) and D17S938 (17p13.1-p13.3) were significantly higher in cases with positive HBsAg than in those with negative HBsAg. Similarly, LOH on loci D1S214 (lp36.3), D1S2797 (1p34) and D3S3681 (3p11.2-p14.2) were more frequently detected in tumors with intrahepatic metastasis than in those without., Conclusions: Status of LOH in HCC in Southern China is similar to that reported previously in other countries and areas. However, we firstly identified high-frequency LOH on chromosome 3p in HCC. Furthermore, HBV infection, as well as tumor intrahepatic metastasis, may be correlated with allelic losses on certain chromosome regions.

The full length of cDNA encoding murine ZAP-70 was obtained from a cDNA library of embryonic mouse thymus. Northern blot analysis indicated that the expression of ZAP-70 mRNA was most pronounced in the thymus and spleen and also slightly in the brain. Analysis by in situ hybridization revealed that the mRNA was expressed not only in T cells in the thymus and spleen, but also in nerve cells of the brain. In the thymus, the distribution of positive cells was different between newborn and young adult mice. In the newborn thymus, positive signal in thymocytes was localized in the subcapsular layer as well as in the medulla, while in the young adult thymus, it was localized exclusively in the medulla. Furthermore, the in situ hybridization revealed that positive signal was also seen in the liver, intestine, and lung of embryonic mice. These findings have suggested that ZAP-70 plays an important role in growth, differentiation, and function of not only T cells but also nerve cells and several embryonic tissues.