RESUMEN
CHI3L1 (YKL40) is a secreted glycoprotein and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in many human cancers. However, the mechanism of how CHI3L1 causes poor prognosis in cancers is still unknown. Here, considering that CHI3L1 is a liver specific/enriched protein, we use hepatocellular carcinoma as a model to study the function of CHI3L1. We showed that, both in vivo and in vitro, overexpression of CHI3L1 could promote liver cancer cells growth, migration and invasion. We then used RNA-seq to analyze the expression profiles of CHI3L1 overexpressed in two HCC cell lines and found that CHI3L1 overexpression affected genes that were involved in cell-cell adhesion, extracellular exosome and adherens junction. Western blot analysis further revealed that CHI3L1 could activate TGF-ß signal pathways. Our data added new understanding of the mechanism of CHI3L1's action. 1) CHI3L1 promoted cancer cell proliferation by regulating cell cycles; 2) CHI3L1 promoted cancer cell invasion and metastasis; 3) CHI3L1 regulate liver cancer potentially by regulating the TGF-ß signaling pathways; 4) CHI3L1 has direct kinase activities or activate kinase to phosphorylate SMAD2, SMAD3.
Asunto(s)
Carcinoma Hepatocelular/genética , Proteína 1 Similar a Quitinasa-3/genética , Neoplasias Hepáticas/genética , Factor de Crecimiento Transformador beta/genética , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Ratones , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Fosforilación , Transducción de Señal , Proteína Smad2/genética , Proteína smad3/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: The primary purpose of this study was to investigate the in vitro and in vivo effect of survivin interference RNA (siRNA) on non-small cell lung cancer. METHODS: Lentivirus was used as a vector to transfer siRNA into human lung cancer A549 cells. The proliferation of the cancer cells was assessed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The lentivirus-mediated siRNA was also injected into the transplanted A549 tumor tissues in mice. Tumour growth was assessed after 11 injections over a period of 21 days. RESULTS: Compared with the placebo and the blank lentiviral vector groups, the siRNA treatment group had reduced cell growth rate following 4 days of the treatment (P < 0.01). The average size of the transplanted A549 tumours in the siRNA treatment group (0.75+/-0.16 cm3, n=8) was smaller than in the placebo (2.09+/-0.22 cm3, n=6) or the blank lentivrial vector groups (1.89+/-0.18 cm3, n=6) (P < 0.01). The tumour growth inhibition rate in the siRNA groups was 46.1%. CONCLUSION: Lentivirus-mediated siRNA therapy inhibits the growth of human lung cancer cells in vitro. The siRNA therapy also suppresses the growth of the transplanted lung cancer in mice.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Proteínas Asociadas a Microtúbulos/genética , Interferencia de ARN , Animales , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular , Cartilla de ADN , Vectores Genéticos , Humanos , Proteínas Inhibidoras de la Apoptosis , Lentivirus/genética , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Reacción en Cadena de la Polimerasa , ARN Interferente Pequeño/genética , SurvivinRESUMEN
The title compound, C(20)H(18)N(2)O, which crystallizes with two independent mol-ecules (A and B) in the asymmetric unit, is composed of three aromatic rings (I, II and III). The conformation of the two independent mol-ecules is slightly different. The dihedral angles between the central aromatic ring II and rings I and III are 47.13â (9) and 89.36â (9)°, respectively, for mol-ecule A, and 29.60â (9) and 70.72â (9)°, respectively, for mol-ecule B. Rings I and III are inclined to one another by 86.57â (9)° in mol-ecule A, and 64.59â (10)° in mol-ecule B. The mol-ecular structures are stabilized by intra-molecular N-Hâ¯O hydrogen bonds. In the crystal structure, mol-ecules are linked through inter-molecular N-Hâ¯O hydrogen bonds, forming chains propagating in the [010] direction. In addition, a number of C-Hâ¯π inter-actions are observed.
RESUMEN
The complete mol-ecule of the title compound, C(26)H(20)N(2)O(3), is generated by crystallographic twofold symmetry, with the central O atom lying on the rotation axis. The conformation is stabilized by an intra-molecular N-Hâ¯O hydrogen bond. The dihedral angle between the inner and outer aromatic ring planes is 61.12â (5)°.