Abstract: In the present invention, it was confirmed that the modified protein in which the 356th serine of Runx3 is substituted with alanine has an increased activity of maintaining the complex with Brd2 by more than 10 times compared to the wild-type Runx3, and the apoptosis effect is improved in various cancer cell lines compared to the wild-type Runx3. Therefore, the modified protein in which the 356th serine of Runx3 is substituted with an amino acid that cannot be phosphorylated by a kinase of the present invention, the polynucleotide coding thereof, the vector carrying the polynucleotide, or the virus or cell transformed with the vector can be used as a therapeutic agent for various cancers.

Abstract: Described herein is an adeno-associated virus (AAV) complex platform including an asymmetrically modified inverted terminal repeat (ITR). The AAV complex has advantages of increased productivity and expression efficiency of a transgene, and decreased genotoxicity, by having an asymmetric ITR in which any one of two ITRs is modified. Also, described herein is a composition comprising the adeno-associated virus complex and a method of gene therapy.

Abstract: Provided is an adeno-associated virus (AAV) complex for expression of an RUNX3 gene including an asymmetrically modified inverted terminal repeat (ITR). The AAV complex has asymmetric ITRs in which one of the two ITRs is modified, thereby increasing self-replication efficiency in host cells and increasing expression efficiency of a delivered gene, and therefore, compared to existing AAV complexes, the AAV complex has an advantage of improved productivity and gene expression efficiency.

Abstract: The present invention relates to a pharmaceutical composition comprising a Runx3 gene or protein as an active ingredient for prevention or treatment of K-Ras mutant lung cancer. Specifically, Runx3 gene-deleted, K-Ras gene-activated lung cancer mice established in the present invention were found to be completely cured without lung cancer recurrence likelihood when restoring the Runx3 gene, compared to the conventional approach of inhibiting the activated cancer gene. Thus, the composition comprising Runx3 protein, a polynucleotide coding therefor, a vector carrying the polynucleotide, or a vims or cell transformed with the vector as an active ingredient according to the present invention can be advantageously used as a composition for prevention or treatment of K-Ras mutant lung cancer.

Abstract: In the present invention, it was confirmed that the modified protein in which the 356th serine of Runx3 is substituted with alanine has an increased activity of maintaining the complex with Brd2 by more than 10 times compared to the wild-type Runx3, and the apoptosis effect is improved in various cancer cell lines compared to the wild-type Runx3. Therefore, the modified protein in which the 356th serine of Runx3 is substituted with an amino acid that cannot be phosphorylated by a kinase of the present invention, the polynucleotide coding thereof, the vector carrying the polynucleotide, or the virus or cell transformed with the vector can be used as a therapeutic agent for various cancers.

Abstract: The present invention relates to a pharmaceutical composition for prevention or treatment of cancer, comprising a Runx3 (Runt-related transcription factor 3) protein, a polynucleotide encoding thereof, a vector carrying the polynucleotide or a virus or cell transformed with the vector; and a CDK4 inhibitor or an mTOR inhibitor as an active ingredient. It was confirmed that the binding of Runx3 and BRD2 was maintained for up to 8 hours when the CDK4 inhibitor (PD0332991) was present at the concentration of 11 nM known to be non-toxic to normal cells. It was also confirmed that the binding of Runx3 and BRD2 was maintained for up to 8 hours when the mTOR inhibitor (rapamycin) was present at the concentration of 100 nM known to be non-cytotoxic to normal cells. In addition, it was confirmed that the cancer apoptotic effect was significantly increased when the CDK4 inhibitor or mTOR inhibitor was administered simultaneously with Runx3 than when Runx3 was administered alone to Runx3 deficient cancer cells.

Abstract: The present invention relates to a method for identifying cells having a predisposition to develop an intestinal phenotype, wherein the cells are characterized by the loss of expression of the RUNX3 gene and the expression of one or more intestinal marker genes. In particular, the invention is directed to the identification of cells, which exhibit an intestinal phenotype representing a precursor of gastric cancer. Furthermore, the invention discloses a method for identifying a compound inhibiting the development of an intestinal phenotype in cells having a predisposition to develop an intestinal phenotype. Finally, the invention also relates to kits of parts for performing these methods.

Abstract: The present invention relates to a method for identifying cells having a predisposition to develop an intestinal phenotype, wherein the cells are characterized by the loss of expression of the RUNX3 gene and the expression of one or more intestinal marker genes. In particular, the invention is directed to the identification of cells, which exhibit an intestinal phenotype representing a precursor of gastric cancer. Furthermore, the invention discloses a method for identifying a compound inhibiting the development of an intestinal phenotype in cells having a predisposition to develop an intestinal phenotype. Finally, the invention also relates to kits of parts for performing these methods.

Abstract: The present invention relates to a RUNX3 gene showing anti-tumor activity which is essentially involved in TGF-?-dependent programmed cell death (apoptosis) and use thereof. In addition, the present invention finds that RUNX3 gene expression is suppressed in the various gastric cancer and lung cancer cell lines. The suppression of the RUNX3 gene expression is due to hyper-methylation of CpG islands located around RUNX3 exon 1. The RUNX3 gene and its gene product of the present invention can be used effectively for the development of anti-cancer agents. The CpG islands around RUNX3 exon 1 could also be used not only for the development of anti-cancer agents which regulate the abnormal DNA methylation and thereby induce RUNX3 expression, and also for the development of methods for cancer diagnosis by measuring the abnormal DNA methylation.

Abstract: The present invention relates to a method to enhance the activity of Runx2, a major target protein of Bone Mophogenetic Protein (BMP), by Runx2 acetylation, more precisely, a method to activate BMP-mediated bone formation pathway by protecting Runx2 from ubiquitination, indicating that Runx2 is protected from degradation by the increase of Runx2 acetylation making the protein more stable. The method to enhance Runx2 activity of the present invention can be utilized for the prevention and the treatment of bone disease such as osteoporosis, osteogenesis imperfecta, periodontal disease and fracture, by inducing bone formation by inhibiting Runx2 degradation.

Abstract: The present invention relates to a RUNX3 gene showing anti-tumor activity which is essentially involved in TGF-? dependent-programmed cell death (apoptosis) and use thereof. In addition, the present invention finds that the RUNX3 gene expression is suppressed in the various gastric cancer and lung cancer cell lines. The suppression of the RUNX3 gene expression is due to hyper-methylation of CpG island located around RUNX3 exon (1). The RUNX3 gene and its gene product of the present invention can be used effectively for the development of anti-cancer agents. CpG island around RUNX3 exon (1) could also be used not only for the development of anti-cancer agents which regulate the abnormal DNA methylation and there by induce RUNX3 expression but also for the development of methods for cancer diagnosis by measuring the abnormal DNA methylation.

Abstract: The present invention relates to a method for identifying cells having a predisposition to develop an intestinal phenotype, wherein the cells are characterized by the loss of expression of the RUNX3 gene and the expression of one or more intestinal marker genes. In particular, the invention is directed to the identification of cells, which exhibit an intestinal phenotype representing a precursor of gastric cancer. Furthermore, the invention discloses a method for identifying a compound inhibiting the development of an intestinal phenotype in cells having a predisposition to develop an intestinal phenotype. Finally, the invention also relates to kits of parts for performing these methods.

Abstract: The present invention relates to a RUNX3 gene showing anti-tumor activity which is essentially involved in TGF-&bgr; dependent-programmed cell death (apoptosis) and use thereof. In addition, the present invention finds that the RUNX3 gene expression is suppressed in the various gastric cancer and lung cancer cell lines. The suppression of the RUNX3 gene expression is due to hyper-methylation of CpG island located around RUNX3 exon (1). The RUNX3 gene and its gene product of the present invention can be used effectively for the development of anti-cancer agents. CpG island around RUNX3 exon (1) could also be used not only for the development of anti-cancer agents which regulate the abnormal DNA methylation and there by induce RUNX3 expression but also for the development of methods for cancer diagnosis by measuring the abnormal DNA methylation.