BackgroundA variety of studies have evaluated the associations between polymorphisms in the promoter regions of Matrix metalloproteinases (MMPs) and cancer metastasis. However, the results remain inconclusive. To better understand the roles of MMP polymorphisms in metastasis, we conducted a comprehensive meta-analysis.MethodsElectronic databases were searched (from January 2000 to June 2011) for any MMP genetic association studies in metastasis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between MMP polymorphisms and metastasis. Statistical analysis was performed with Review Manager 5.0 and STATA11.0.ResultsThirty-three studies addressing five MMP polymorphisms were analyzed among 10,516 cancer cases (4,059 metastasis-positive cases and 6,457 metastasis-negative cases). For MMP1 (−1607)1G/2G, genotype 2G/2G increased the overall risk of metastasis under the recessive model (OR = 1.44, 95% CI = 1.05–1.98). In subgroup analysis based on cancer type, associations were found in head/neck and breast cancer under the recessive model, and also in breast cancer under the dominant model. For MMP3 (−1171) 5A/6A, the polymorphism decreased the overall risk of metastasis under two genetic models (recessive: OR = 0.80, 95%CI = 0.64–0.99, dominant: OR = 0.72, 95%CI = 0.56–0.93). The polymorphisms of MMP7 (−181) A/G and MMP9 (−1562) C/T increased metastatic risk. However, no association was observed between MMP2 (−1306) C/T and metastasis.ConclusionsOur investigations demonstrate that polymorphisms in the promoter regions of MMP1, 3, 7 and 9 might be associated with metastasis in some cancers. Further studies with large sample size for MMP2 should be conducted.

Dendrobium officinale L. is an important traditional herb with high commercial value in China. Several bioactive constituents, including polysaccharides and alkaloids, reportedly make major contributions toward the excellent medicinal effect of D. officinale. In this study, the contents of polysaccharides and alkaloids in various organs of D. officinale were measured and compared. We took advantage of transcriptomes from four organs to explore biological mechanisms in the organ-specific distribution of active ingredients in D. officinale. Based on Kyoto Encyclopedia of Genes and Genomes pathways, unigenes related to the enzymes involved in fructose and mannose metabolism and unigenes associated with putative upstream elements of the alkaloid biosynthetic pathway were identified. A large number of candidates, including 35 full-length glycosyltransferase genes and 49 full-length P450 genes, were also identified based on the transcriptome data, and the organ-specific expression pattern of these genes was determined. Furthermore, differential expression of all candidate genes was analyzed in two Dendrobium species, D. nobile L. and D. officinale. The data will supply important clues to exploit useful genes involved in polysaccharide and alkaloid synthesis.

Upregulation of long non-coding RNA LINC00963 has been observed in several cancer types. In this study, we analyzed the clinical and biological significance of LINC00963 in breast cancer. The key microRNA (miR) mediating the action of LINC00963 was identified. We show that LINC00963 upregulation is correlated with aggressive parameters of breast cancer. Silencing of LINC00963 suppresses the proliferation and tumorigenesis of breast cancer cells, whereas LINC00963 overexpression exerts an opposite effect. Knockdown of LINC00963 enhances DNA damage and oxidative stress and sensitizes breast cancer cells to radiation. Mechanistically, LINC00963 antagonizes the repressive activity of miR-324-3p on ACK1 expression. Clinically, there is a negative correlation between miR-324-3p and LINC00963 expression in breast cancer tissues. Overexpression of LINC00963 or ACK1 rescues the inhibitory effects of miR-324-3p on breast cancer cell proliferation and radiosensitivity. In addition, knockdown of ACK1 attenuates LINC00963-dependent breast cancer growth and tumorigenesis. Taken together, LINC00963 promotes tumorigenesis and radioresistance in breast cancer through interplay with miR-324-3p and derepression of ACK1. LINC00963 may represent a potential target for the treatment of breast cancer.

Several phytohormones have been demonstrated to be involved in iron (Fe) homeostasis. We took advantage of a salicylic acid (SA) biosynthesis defective mutant phytoalexin deficient 4 (pad4: T-DNA Salk_089936) to explore the possible effects of endogenous SA on the morphological and physiological responses to Fe deprivation. The morphological and physiological analysis was carried out between Col-0 and the pad4 mutant. Under an Fe-deficiency treatment, Col-0 showed more severe leaf chlorosis and root growth inhibition compared with the pad4 mutant. The soluble Fe concentrations were significantly higher in pad4 than in Col-0 under the Fe-deficiency treatment. Fe deficiency significantly induced SA accumulation in Col-0 and the loss-of-function of PAD4 blocked this process. The requirement of endogenous SA accumulation for Fe-deficiency responses was confirmed using a series of SA biosynthetic mutants and transgenic lines. Furthermore, a comparative RNA sequencing analysis of the whole seedling transcriptomes between Col-0 and the pad4 mutant was also performed. Based on the transcriptome data, the expression levels of many auxin- and ethylene-response genes were altered in pad4 compared with Col-0. Fe deficiency increases SA contents which elevates auxin and ethylene signalling, thereby activating Fe translocation via the bHLH38/39-mediated transcriptional regulation of downstream Fe genes.

Taxol is currently a valuable anticancer drug; however, the accumulated mixture of taxoids can vary greatly among Taxus species. So far, there is very little genomic information for the genus Taxus, except for Taxus baccata. Transcriptome analysis is a powerful approach to explore the different regulatory mechanisms underlying the taxoid biosynthesis pathway in Taxus species. First, we quantified the variation in the taxoid contents between Taxus media and Taxus mairei. The contents of paclitaxel and 10-deacetylpaclitaxel in T. media are higher than that in T. mairei. Then, the transcriptome profiles of T. media and T. mairei were analyzed to investigate the altered expressions. A total of 20,704 significantly differentially expressed genes (DEGs), including 9865 unigenes predominantly expressed in T. media and 10,839 unigenes predominantly expressed in T. mairei, were identified. In total, 120 jasmonic acid-related DEGs were analyzed, suggesting variations in 'response to JA stimulus' and 'JA biosynthetic process' pathways between T. media and T. mairei. Furthermore, a number of genes related to the precursor supply, taxane skeleton formation and hydroxylation, and C13-side chain assembly were also identified. The differential expression of the candidate genes involved in taxoid biosynthetic pathways may explain the variation in the taxoid contents between T. media and T. mairei.

Taxus species are well-known for paclitaxel, which exhibits antitumor activities and is used for treating various cancers. Although most Taxus species are widespread in many areas, few studies have characterized the variation in metabolism among different Taxus species. Using an integrated approach involving 'tandem mass tag' labeling and liquid chromatography-tandem mass spectrometry (HPLC-MS), proteomes of T. media and T. mairei were investigated and 4078 proteins were quantified. Screening and classification of differentially expressed proteins revealed many metabolism-associated proteins. In detail, four enzymes involved in the flavonoid biosynthesis pathway were predominantly expressed in T. mairei. Four enzymes associated with supplying precursors for paclitaxel biosynthesis and three cytochrome P450 taxoid oxygenases were preferentially expressed in T. media compared with T. mairei. Furthermore, variations in taxoid contents between T. media and T. mairei were determined using HPLC-MS analysis. Variations in flavonoid contents between T. media and T. mairei were determined by HPLC analysis. A number of differentially expressed proteins may provide an explanation for the variation in metabolisms of different Taxus species.

Protein lysine succinylation, a ubiquitous protein post-translational modification among eukaryotic and prokaryotic cells, represents a vital regulator of various metabolic processes. However, little is known about its functions and cellular distribution in Taxus × media, which is a hybrid Taxus species containing a high content of taxol. In this study, LC-MS/MS was used to identify peptides enriched by immune-purification with high-efficiency succinyl-lysine antibody. A total of 193 succinylated proteins and 325 succinylation sites were identified. The bioinformatics analysis indicated that these succinylated proteins were involved in a wide range of cellular functions from metabolism to protein binding and showed diverse subcellular localizations. Furthermore, our findings suggested that lysine succinylation in Taxus × media involved a diverse array of metabolic processes and protein–protein interactions. Many enzymes involved in multiple metabolic pathways, such as glycolysis, pyruvate metabolism, the tricarboxylic acid cycle and carbon fixation, were identified as substrates for lysine succinylation, suggesting the presence of a common mechanism underlying the participation of succinylation in metabolic regulation. These results provide the first comprehensive view of the succinylome of Taxus × media and may catalyze future biological investigation of succinylation.

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