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Background: Matrix metalloproteinases (MMPs) are capable of degrading and modifying most components of the extracellular matrix (ECM) and the basal membrane (BM), and play crucial roles in cancer invasion and metastasis. MMP gene expressions were regulated primarily at the transcriptional level, which was associated with tumor spread and patient prognosis. Polymorphisms in MMPs have been reported to be associated with non-small cell lung cancer (NSCLC). The objective of this study aim to evaluate the serum levels and polymorphisms of MMP-9 and MMP-13 in non-small cell lung cancer patients compared to normal subjects and their correlation to non-small cell lung cancer histopathology findings in Southern Chinese people. Methods: This case–control study included 245 patients with NSCLC and 258 healthy controls. Genomic DNA was extracted by using DNA extraction kit, genotyping was confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing, and serum levels of MMP-9 and MMP-13 were measured by using a specific ELISA, Human Matrix Metalloproteinase Enzyme Immunoassay Kits. Statistical analysis was carried out using the SPSS 23.0 software package. Results: The subjects carrying the TT genotype had a decreased risk of lung cancer in MMP9-1562C/T comparing with the CC genotype (p = 0.00, OR = 0.45, 95% CI = 0.29–0.68), and the MMP13-77 AA genotype was associated with a decreased risk of NSCLC by comparing with the GG genotype (p = 0.03, OR = 0.56, 95% CI = 0.33–0.94). Moreover, the C allele of MMP9-1562C/T could increase serum level of NSCLC in compared with the A allele (OR = 1.19, 95% CI = 0.75–1.89). Similarly, the AA genotype of MMP13 might be a marker of decreased serum level of lung cancer (OR = 0.76, 95% CI = 0.51–1.14). Conclusions: The results of these analyses underline the support of the notion that the CC genotype of MMP9-1562C/T and GG genotypes of MMP13-77G/A were associated with the increased risk NSCLC, and the serum levels of MMP9 and MMP13 were consistent with the results of the SNP analysis. MMP13 and MMP9 might be function as a key oncogene in NSCLC with a Southern Chinese population. Combined detection of SNP and enzyme activity between MMP9 and MMP13 are expected to be a potential diagnostic method of non-small cell lung cancer.

Calponin 2 (h2 calponin, CNN2) is an actin-binding protein implicated in cytoskeletal organization. We have found that the expression of calponin 2 is relatively restricted to vasculature from 16 to 30 h post-fertilization during zebrafish (Danio rerio) development. Forty-eight hours after injecting antisense morpholino oligos against calponin 2 into embryos at the 1-4-cell stage, zebrafish demonstrated various cardiovascular defects, including sluggish axial and head circulation, absence of circulation in intersegmental vessels and in the dorsal longitudinal anastomotic vessel, enlarged cerebral ventricles, and pericardial edema, in addition to an excess bending, spiraling tail and twisting of the caudal fin. Knockdown of calponin 2 in the Tg(fli1:EGFP) y1 zebrafish line (in which a fli1 promoter drives vascular-specific enhanced green fluorescent protein expression) indicated that diminished calponin 2 expression blocked the proper migration of endothelial cells during formation of intersegmental vessels. In vitro studies showed that basic fibroblast growth factor-induced human umbilical vein endothelial cell migration was down-regulated by knockdown of calponin 2 expression using an antisense adenovirus, and overexpression of calponin 2 enhanced migration and hastened wound healing. These events were correlated with activation of mitogen-activated protein kinase; moreover, inhibition of this pathway blocked the promigratory effect of calponin 2. Collectively, these data suggest that calponin 2 plays an important role in the migration of endothelial cells both in vivo and in vitro and that its expression is critical for proper vascular development.Calponin 2 is a member of the calponin family, which includes two other distinct members, basic calponin 1 (h1 calponin, CNN1) (1) and acidic calponin 3 (h3 calponin, CNN3) (2). These calponins share high sequence homology at the amino-terminal two-thirds of the molecule, which contains the calponin homology (CH) 3 domain followed by three calponin repeats (3, 4). The carboxyl-terminal sequences beyond Cys-273 are unique for the three variants, accounting for differences in their isoelectric points. Calponin 1 is specific to smooth muscle cells and serves as a marker for smooth muscle cell differentiation. It inhibits the actin-activated ATPase activity of myosin (5) and may play a role in regulating smooth muscle contraction. As an actin-, tropomyosin-and calmodulin-binding protein, it interacts in vitro with cytoskeletal components, such as myosin (6, 7), caldesmon (8, 9), desmin (10), and tubulin (11). Calponin 1 has been shown to play an important role in agonist-induced signal transduction in smooth muscle cells (12). It binds to extracellular regulated Ser/Thr kinases (ERK1 and ERK2) (13, 14) through the aminoterminal CH domain and protein kinase C (PKC) (15).Less is known about the function of calponin 2. Although the sequence conservation between calponin 2 and calponin 1 points to a similar function, they have diverged during vertebrate evolution, and the se...