Specification of the myriad of unique neuronal subtypes found in the nervous system depends upon spatiotemporal cues and terminal selector gene cascades, often acting in sequential combinatorial codes to determine final cell fate. However, a specific neuronal cell subtype can often be generated in different parts of the nervous system and at different stages, indicating that different spatiotemporal cues can converge on the same terminal selectors to thereby generate a similar cell fate. However, the regulatory mechanisms underlying such convergence are poorly understood. The Nplp1 neuropeptide neurons in the Drosophila ventral nerve cord can be subdivided into the thoracic-ventral Tv1 neurons and the dorsal-medial dAp neurons. The activation of Nplp1 in Tv1 and dAp neurons depends upon the same terminal selector cascade: colamp;gt;ap/eyaamp;gt;dimmamp;gt;Nplp1. However, Tv1 and dAp neurons are generated by different neural progenitors (neuroblasts) with different spatiotemporal appearance. Here, we find that the same terminal selector cascade is triggered by Kr/pdmamp;gt;grn in dAp neurons, but by Antp/hth/exd/lbe/cas in Tv1 neurons. Hence, two different spatiotemporal combinations can funnel into a common downstream terminal selector cascade to determine a highly related cell fate.

Background: Astrocyte elevated gene 1 (AEG-1), an important oncogene, has been shown to be overexpressed in several types of cancers. In colorectal cancer (CRC), the protein level of AEG-1 is up-regulated in tumour tissue compared to normal mucosa, showing prognostic significance. Since little is known about the transcriptional level of AEG-1 expression and its biological pathway in CRC the aim of the present study was to examine the relationship of AEG-1 mRNA expression, the protein level and clinicopathological variables as well as its biology pathway in CRC. less thanbrgreater than less thanbrgreater thanMaterial and methods: The mRNA expression of AEG-1 was analysed by qPCR in fresh frozen patient samples including 156 primary tumours, along with the corresponding normal mucosa, and in five colon cancer cell lines, SW480, SW620, KM12C, KM12SM and KM12L4a. AEG-1 protein expression was investigated by immunohistochemistry in paraffin-embedded materials from 74 distant normal mucosa, 107 adjacent mucosa, 158 primary tumour, 35 lymph node metastasis and 9 liver metastasis samples. In addition, the AEG-1 protein expression was elucidated in the cell lines by Western blot. less thanbrgreater than less thanbrgreater thanResults: The lymph node metastatic cell line SW620 had a significantly higher AEG-1 mRNA (0.27 +/- 0.02) expression compared to the primary tumour cell line SW480 (0.17 +/- 0.04, p = 0.026). AEG-1 expression at the mRNA level and/or the protein level was significantly up-regulated gradually from normal mucosa to primary CRC, and then to lymph node metastasis and finally to liver metastasis (p andlt; 0.05). There were significant associations of AEG-1 mRNA expression with tumour location (p = 0.047), as well as mRNA and protein expression with the tumour stage (p andlt; 0.03). Furthermore AEG-1 protein expression was positively related to biological variables including NF-kappa B, p73, Rad50 and apoptosis (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: AEG-1 is up-regulated, at the mRNA and the protein level, during CRC development and aggressiveness, and is related to tumour location and stage. It may play its role in CRC through the NF-kappa B signaling pathway.

Background: MicroRNAs (miRNAs) are endogenously expressed noncoding RNAs with important biological and pathological functions. Although several studies have shown that microRNA-31 (miR-31) is obviously up-regulated in colorectal cancer (CRC), there is no study on the functional roles of miR-31 in CRC. Methods: Anti-miR (TM) miRNA 31 inhibitor (anti-miR-31) is a sequence-specific and chemically modified oligonucleotide to specifically target and knockdown miR-31 molecule. The effect of anti-miR-31 transfection was investigated by real-time PCR. HCT-116(p53+/+) and HCT-116(p53-/-)colon cancer cells were treated by anti-miR-31 with or without 5-fluorouracil (5-FU), cell proliferation was determined by MTT assay; apoptosis was detected by DAPI staining; cell cycle was evaluated by flow cytometry; colony formation, migration and invasion assays were performed to investigate the effect of suppression of miR-31 on the cell lines. Results: Real-time PCR results showed that anti-miR-31 was efficiently introduced into the cells and reduced miR-31 levels to 44.1% in HCT-116(p53+/+) and 67.8% in HCT-116p(53-/-)cell line (p = 0.042 and 0.046). MTT results showed that anti-miR-31 alone had no effect on the proliferation of HCT-116(p53+/+) or HCT-116(p53-/-). However, when combined with 5-FU, anti-miR-31 inhibited the proliferation of the two cell lines as early as 24 h after exposure to 5-FU (p = 0.038 and 0.044). Suppression of miR-31 caused a reduction of the migratory cells by nearly 50% compared with the negative control in both HCT-116(p53+/+) and HCT-116(p53-/-)(p = 0.040 and 0.001). The invasive ability of the cells were increased by 8-fold in HCT-116(p53+/+) and 2-fold in HCT-116(p53-/-)(p = 0.045 and 0.009). Suppression of miR-31 had no effect on cell cycle and colony formation (p andgt; 0.05). Conclusions: Suppression of miR-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells.