Project description:Soft tissue sarcoma (STS) is a group of malignancies that can appear in any part of the body. The prognosis of STS patients remains unsatisfactory, mainly due to metastasis and recurrence. Upregulation of KIF20A is associated with poor prognosis of STS patients, but its downstream mechanism is unknown. In the present study, we found that downregulation of KIF20A in the STS cell line HT-1080 inhibits cell proliferation, migration, and invasion and induced cell apoptosis and G2/M arrest in vitro. In addition, downregulation of KIF20A in HT-1080 repressed tumorigenesis of STS in a xenograft mouse model. Pathway analysis showed, that downregulation of KIF20A led to suppression of downstream PI3K-AKT and NF-κB pathways. Specifically, the phosphorylation of AKT at Ser473 was inhibited. Taken together, our results indicate that KIF20A plays an important role in the development of STS by inhibiting cell proliferation, migration, invasion via the PI3K-AKT signaling pathway. Therefore, KIF20A is a potential therapeutic target in STS.
Project description:Abstract Aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis primarily in estrogen receptor positive (ER(+)) breast cancers and activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of *STAT3* in ER(+) breast cancers are* *through multiple interacting regulatory pathways including STAT3-MYC, STAT3-ER , STAT3-MYC-ER interactions and the direct action of activated STAT3. These results predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ER and STAT3 in regulating their shared target gene-*METAP2* is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the *STAT3* network and a robust one in a subset of patients. *VEGFA*, *ABL1*, *LYN*, *IGF2R* and* STAT3* are suggested therapeutic targets for further study based upon the degree of differential expression in our model. Keywords: STAT3 transcriptional regulatory network, prognosis, tamoxifen resistance, tumorigenesis, breast cancer.
Project description:Balanced symmetric and asymmetric divisions of neural progenitor cells (NPCs) are crucial for orderly progression of brain development, but the underlying mechanisms are not fully understood. Here, we report that mitotic kinesin KIF20A/MKLP2 interacts with RGS3 and plays a crucial role in controlling the division modes of NPCs during the mouse cortical neurogenesis. KIF20A is selectively expressed by daughter progenitors in NPC divisions. Knockdown of KIF20A causes dislocation of RGS3 from the intercellular bridge (ICB) of dividing NPCs, impairs the function of EphrinB-RGS cell fate signaling complex, and leads to a transition in NPCs from proliferative to differentiative divisions. Germ-line and inducible knockout of KIF20A causes a loss of progenitor cells and neurons and results in thinner cortex and ventriculomegaly. Interestingly, loss-of-function of KIF20A induces early cell cycle exit and precocious neuronal differentiation without causing substantial multinucleation or apoptosis in mutant NPCs. Our results thus uncover a novel RGS-KIF20A axis in regulation of cell division mode and suggest a potential link of cytokinesis control within the ICB to regulation of cell fate determination.
Project description:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. It is crucial to identify patients with a high risk of recurrence and develop more intensified or targeted treatment strategy to improve disease outcome. In the training set, tumor and non-tumor liver were profiled separately, and each was used to generate a prediction model which was validated with the use of independent validation set.
Project description:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis, which correlate with recurrence after surgical treatment and poor prognosis. It is crucial to identify patients with a high risk of recurrence and develop more intensified or targeted treatment strategy to improve disease outcome.
Project description:Aberrations in the Hedgehog (Hh) pathway are known to related to several malignancies. However, little is known about the function of GLI2, a transcription factor in the Hh pathway, in osteosarcoma. Osteosarcoma is the most frequent primary bone sarcoma in children and adolescents. Despite survival rates of osteosarcoma patients have increased, the prognosis of patients with metastasis remains poor. Therefore, the development of novel therapeutic strategies for osteosarcoma patients is development of novel therapeutic strategies for osteosarcoma patients is urgently needed. Aberrations in the Hedgehog (Hh) pathway are known to related to several malignancies. However, little is known about the function of GLI2, a transcription factor in the Hh pathway, in osteosarcoma. Our findings revealed that GLI2 was overexpressed in osteosarcoma tissues. Additionally, GLI2 is involved in the metastasis of osteosarcoma cells through the regulation of ribosomal protein S3 expression. Furthermore, we showed that arsenic trioxide (ATO) suppressed the invasion and lung metastasis of osteosarcoma cells by the inhibition of GLI transcription. Consequently, these finding reveal a novel function of GLI2 in the metastasis of osteosarcoma and that ATO may be a new therapeutic agentay be a new therapeutic agent. We revealed that a novel function of GLI2 in the metastasis of osteosarcoma and that ATO may be a new therapeutic agent for preventing osteosarcoma metastasis. Negative siRNA(U-2OS) and GLI2 siRNA(U-2OS)
