Zheng-Shi Wang

MicroRNA-187 inhibits tumor growth and invasion by directly targeting CD276 in colorectal cancer.

Aberrantly expressed microRNAs contribute to the initiation and progression of human cancers. However, the underlying functions of microRNA-187 (miR-187) in colorectal cancer (CRC) remain largely unexplored. Here, we demonstrated that miR-187 was significantly down-regulated in CRC tissues and cell lines compared to their normal counterparts. By Kaplan-Meier analysis, we revealed that decreased miR-187 expression was closely associated with shorter overall survival and relapse-free survival of patients with CRC. By gain- and loss-of-function studies, we showed that miR-187 remarkably suppressed CRC cell proliferation, migration, invasion, and promoted cell apoptosis. Furthermore, bioinformatics analysis and luciferase reporter assay identified that CD276 was the direct functional target of miR-187 in CRC. Genetic silencing of CD276 recapitulated similar phenotype as observed in over-expression of miR-187, and restoration of CD276 completely rescued the inhibitory effect of miR-187 in CRC cells. Taken together, our study implied the essential roles of miR-187 in suppressing CRC progression, and a novel link between miR-187 and CD276 in CRC.

Elevated expression of ECT2 predicts unfavorable prognosis in patients with colorectal cancer.

Epithelial cell transforming sequence 2 (ECT2) is a well-studied guanine nucleotide exchange factor for the Rho family GTPase, which has been demonstrated as an oncogene in many types of human cancers. However, little is known about the prognostic value of ECT2 in colorectal cancer (CRC). In current study, we investigated the expression pattern and underlying clinical significance of ECT2 in CRC. ECT2 expression was detected in 345 CRC specimens by immunohistochemistry, and its correlation with clinicopathologic parameters and prognosis of CRC patients were analyzed. Data from Oncomine database and real-time PCR demonstrated that ECT2 expression was elevated in CRC compared with normal tissues. Among the clinical parameters analyzed, high expression level of ECT2 significantly associated with tumor size (P=0.020), serum CEA levels (P = 0.000) and TNM stage (P=0.027). Kaplan-Meier survival analysis showed that patients with high ECT2 expression had a remarkably shorter overall survival. Cox regression analysis revealed that ECT2 expression level was a significant and independent prognostic factor for overall survival rate of CRC patients. These data suggested that ECT2 is an unfavorable biomarker of prognosis in CRC and that ECT2 may be a potential therapeutic candidate for CRC treatment.

Prognostic value of regulator of G-protein signaling 6 in colorectal cancer.

Reprogrammed metabolism is a hallmark of cancer cells. Regulator of G-protein signaling 6 (RGS6), which is frequently down-regulated in multiple human malignancies, has been demonstrated to play a critical function in energy metabolism, cell apoptosis and tumorigenesis. However, limited knowledge is known about the expression pattern and prognostic value of RGS6 in colorectal cancer (CRC). In this study, we first observed that RGS6 mRNA and protein is commonly downregulated in 32 paired CRC tissues compared with their normal counterparts. Furthermore, by a large scale of immunohistochemical analysis in a tissue microarray containing 310 cases of CRC specimens, we demonstrated that the protein expression of RGS6 expression is downregulated in 40.97% (127/310) samples and detected that decreasing RGS6 expression is closely correlated with enhanced tumor size, CEA level, T classification, TNM stage, and easier lymphatic and distant metastasis. Meanwhile, Kaplan-Meier survival analysis showed that CRC patients with a lower RGS6 expression have a poorer clinical outcome than those with a higher RGS6 expression. Multivariate Cox regression analysis revealed that RGS6, lymphatic metastasis and distant metastasis are the independent prognostic factors for overall survival rate of CRC patients. Taken together, our studies reveal the prognostic value of RGS6 in CRC and support that RGS6 may act as a molecular target for CRC treatment.

Evidence of positive selection at signal peptide region of interferon gamma

Interferon gamma (IFNG) is a major cytokine and plays crucial roles in pathogen clearance. About the course of evolution of IFNG, it has been reported that IFNG is being subjected to adaptive selection, which is proved at the level of gene. Neighbor-joining method was used to reconstruct the phylogenetic tree of all IFNG protein-coding sequences. The pair-wise computation of Ka/Ks between every exon homologs, branch-specific model, and site-specific model of the likelihood method were performed to detect positive selection of IFNG. We reported, for the first time, that the signal peptide region of IFNG is under significant positive selection, evolving faster than other parts. We provide evidence at the level of individual exon and individual amino acid site that IFNG is under adaptive evolution, which establishes the basis for further researches about IFNG.

Signatures of positive selection in LY96 gene in vertebrates

As a secreted glycoprotein that binds to the extracellular domain of Toll-like receptor 4 (TLR4), Lymphocyte Antigen 96 (LY96), also called myeloid differentiation 2 (MD2), is required for the activation of TLR4 by lipopolysaccharide (LPS) and plays an important role in innate immunity, which is the first line of defence against microbial infections. Previous studies have proposed that mammalian toll-like receptors (TLRs) have evolved under diversifying selection due to their role in pathogen detection. Given the fact that LY96 is highly functionally linked to TLR4, it would be interesting to test whether LY96 is under the intense pressure of natural selection. To investigate the natural selection hypothesis, we compared the coding sequences from 13 vertebrates and evaluated the molecular evolution of LY96 gene in these species. Result shows that natural selection at exon 4 has indeed played a role in shaping the function of LY96 in the course of evolution. In addition to the study of Nakajima, we found the two branch nodes with Ka/Ks ratios greater than 1: the one leading to cow and pig and the other to rabbit and the primates.