Similar Datasets
Project description:Transcriptional regulation is critically involved in colorectal cancer (CRC) pathogenesis, the mechanism of which remains incompletely understood. Here, we report that core-binding factor β (CBFβ) is commonly upregulated in human colorectal cancer and is associated with the survival rate of CRC patients. Immunohistochemistry (IHC) analysis of RUNX1-3 expression in CRC patients and other in vitro data revealed that CBFβ promotes cell proliferation and liver metastasis in a RUNX2-dependent way. Transcriptome sequencing, ChIP-seq and promoter-binding experiments demonstrated that the CBFβ/RUNX2 complex could activate the transcription of OPN, FAM129A and UPP1. Furthermore, CBFβ significantly promoted tumor growth and lung metastasis in a mouse xenograft model and an orthotopic liver metastasis model of CRC. Additionally, we identified that tumor-suppressive miR-143/145 could synergistically target CBFβ by specifically binding to its 3’-UTR region. An inverse correlation between miR-143/145 and CBFβ was verified in CRC patients. Our results represent the first report describing a mechanistic role for CBFβ-RUNX2 in the transcriptional activation of OPN, FAM129A and UPP1 in controlling colorectal cancer development, which may offer prognostic and therapeutic opportunities.
2021-11-10 | GSE153682 | GEO
Project description:Transcriptional regulation is critically involved in colorectal cancer (CRC) pathogenesis, the mechanism of which remains incompletely understood. Here, we report that core-binding factor β (CBFβ) is commonly upregulated in human colorectal cancer and is associated with the survival rate of CRC patients. Immunohistochemistry (IHC) analysis of RUNX1-3 expression in CRC patients and other in vitro data revealed that CBFβ promotes cell proliferation and liver metastasis in a RUNX2-dependent way. Transcriptome sequencing, ChIP-seq and promoter-binding experiments demonstrated that the CBFβ/RUNX2 complex could activate the transcription of OPN, FAM129A and UPP1. Furthermore, CBFβ significantly promoted tumor growth and lung metastasis in a mouse xenograft model and an orthotopic liver metastasis model of CRC. Additionally, we identified that tumor-suppressive miR-143/145 could synergistically target CBFβ by specifically binding to its 3’-UTR region. An inverse correlation between miR-143/145 and CBFβ was verified in CRC patients. Our results represent the first report describing a mechanistic role for CBFβ-RUNX2 in the transcriptional activation of OPN, FAM129A and UPP1 in controlling colorectal cancer development, which may offer prognostic and therapeutic opportunities.
2021-11-10 | GSE153642 | GEO
Project description:CBFβ promotes colorectal tumor growth and metastasis in a RUNX2-dependent manner
| PRJNA647623 | ENA
Project description:CBFβ promotes colorectal tumor growth and metastasis in a RUNX2-dependent manner (ChIP-seq)
| PRJNA643684 | ENA
Project description:CBFβ promotes colorectal tumor growth and metastasis in a RUNX2-dependent manner (RNA-seq)
| PRJNA643529 | ENA
Project description:Colorectal cancer (CRC) is commonly associated with aberrant transcription regulation, but characteristics of the dysregulated transcription factors in CRC pathogenesis remain to be elucidated. In the present study, core-binding factor β (CBFβ) is found to be significantly upregulated in human CRC tissues and correlates with poor survival rate of CRC patients. Mechanistically, CBFβ is found to promote CRC cell proliferation, migration, invasion, and inhibit cell apoptosis in a RUNX2-dependent way. Transcriptome studies reveal that CBFβ and RUNX2 form a transcriptional complex that activates gene expression of OPN, FAM129A, and UPP1. Furthermore, CBFβ significantly promotes CRC tumor growth and live metastasis in a mouse xenograft model and a mouse liver metastasis model. In addition, tumor-suppressive miR-143/145 are found to inhibit CBFβ expression by specifically targeting its 3'-UTR region. Consistently, an inverse correlation between miR-143/miR-145 and CBFβ expression levels is present in CRC patients. Taken together, this study uncovers a novel regulatory role of CBFβ-RUNX2 complex in the transcriptional activation of OPN, FAM129A, and UPP1 during CRC development, and may provide important insights into CRC pathogenesis.
| S-EPMC8563980 | biostudies-literature
Project description:SOX8 plays an important role in several physiological processes. Its expression is negatively associated with overall survival in patients with colorectal carcinoma (CRC), suggesting SOX8 is a potential prognostic factor for this disease. However, the role of SOX8 in CRC remains largely unknown. In this study, our data showed that SOX8 expression was upregulated in CRC cell lines and tumor tissues. Stable knockdown of SOX8 in CRC cell lines dramatically reduced cell proliferation, migration, and invasion. Furthermore, the knockdown of SOX8 decreased the phospho-GSK3β level and suppressed Frizzled-6 (FZD6) transcription; restoration of FZD6 expression partially abolished the effect of SOX8 on Wnt/β-catenin signaling and promote CRC cell proliferation. In conclusion, our findings suggested that SOX8 served as an oncogene in CRC through the activation of FZD6-dependent Wnt/β-catenin signaling.
| S-EPMC10686890 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-08-02 | GSE182467 | GEO
Project description:GRHL3 is a factor associated with a tumor, of which the molecular mechanism remains a further investigation. We explored the underlying mechanism of tumor-promoting effect of GRHL3 in colorectal cancer (CRC), which is involved in the MEK1/2 pathway. The expression of GRHL3 was measured in CRC and adjacent normal tissue using qPCR and immunohistochemical staining. Lentivirus-mediated knockdown expression of GRHL3 was performed in the CRC cell line HT29. Cell proliferation and metastasis were assayed in vitro, and tumorigenicity was investigated in vivo. We found higher GRHL3 expression in colorectal cancer, which was negatively correlated with patients' prognosis. Results from studies in vitro and in vivo indicated that downregulation of GRHL3 expression inhibited tumor growth and metastasis and inhibited the activation of the MEK1/2 pathway. The effect of GRHL3 downexpression was the same as that of MEK1/2 antagonists on suppression of tumor growth and metastasis. Our results suggested that GRHL3 may act as an oncogene to promote tumor growth and metastasis via the MEK pathway in colorectal cancer.
| S-EPMC8651427 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) infection. Myeloid-specific S100 proteins (S100s), namely, S100A8, S100A9 and S100A12, have been recently recognized as newly discovered damage-associated molecular patterns (DAMPs) that are correlated with progression in pathogen of infectious diseases. However, whether S100s are regulated by HBV and involved in HBV-related hepatocarcinogenesis are still unclear. Here, we found that all expression levels of myeloid-specific S100s (S100A8, S100A9 and S10012) were elevated in serum and tissue samples from HCC patients. Expression of S100A9 but not S100A8 and S10012 were also higher in blood serum and tissue samples from HBV-positive HCC patients than that in HBV-negative HCC patients. High levels of intracellular and extracellular S100A9 were also confirmed in HepG2 cells expressing 1.3-fold HBV genome or HBV-encoded X protein (HBx) as well as in a stable HBV-producing cell line HepG2.2.15. HBx was shown to facilitate translocation of NF-κB from the cytoplasm to the nucleus, and NF-κB bound to the promoter of S100A9 to enhance its transcription. Silencing S100A9 expression partially blocked HBx-induced growth and metastasis of HepG2 cells both in vitro and in vivo. Further, serum S100A9 levels were found to correlate with TNM stage, extrahepatic metastasis status and HBV DNA load in HBV-related HCC and also had a better diagnostic value for identifying extrahepatic metastasis. Our these data demonstrate that S100A9 plays a pivotal role in HBx-induced growth and metastasis of HCC and may serve as a potential diagnostic marker for extrahepatic metastasis.
| S-EPMC5967311 | biostudies-literature