Related Experiment Video
Updated: Aug 24, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Silencing of KNTC1 inhibits hepatocellular carcinoma cells progression via suppressing PI3K/Akt pathway
Hui Tong1, Xiaohui Liu2, Chenghong Peng1
1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Abstract:
Kinetochore associated 1 (KNTC1) encodes a kinetochore component in Rod-Zwilch-ZW10 (RZZ) complex which is essential for the segregation of sister chromatids during mitosis and participates in the spindle checkpoint. Recent research demonstrated that kinetochore proteins may be potential biomarkers and may contribute to the development of human malignancies. Our immunohistochemistry experiment showed that KNTC1 was highly expressed in hepatocellular carcinoma (HCC) tissues and correlated with terrible prognosis, indicating that KNTC1 acts a pivotal role in HCC development. Furthermore, lentivirus delivered short hairpin RNA (shRNA) KNTC1 (Lv-shKNTC1) was applied to infect BEL-7404 and SK-HEP-1 to identify roles of KNTC1 on HCC. Lv-shKNTC1 cells showed reduced proliferation ability, increased apoptosis and decreased migration ability. In vivo experiments suggested that xenografts grow significantly slower upon the silencing of KNTC1. Mechanistically, the protein levels of PIK3CA, p-Akt, CCND1, CDK6 are all down-regulated in Lv-KNTC1 cells and the Lv-shKNTC1 tumor tissues of nude mice. Therefore, KNTC1 may affect the biological activity of HCC cells through PI3K/Akt signaling pathway. Further studies revealed that ZW10 is a pivotal protein that participates in KNTC1-induced regulation of PI3K/Akt signaling pathway. In summary, the key finding of this report highlighted the significance of KNTC1 in tumor regression of HCC, demonstrating KNTC1 as an innovative target for adjuvant treatment of HCC.
Insights
Kinetochore associated 1 (KNTC1) promotes hepatocellular carcinoma (HCC) growth by regulating the PI3K/Akt pathway. Silencing KNTC1 inhibits HCC progression, offering a potential therapeutic target for this cancer.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Kinetochore proteins, like KNTC1, are crucial for mitosis and spindle checkpoint control.
- Aberrant expression of kinetochore proteins is implicated in various human malignancies.
- KNTC1's role in hepatocellular carcinoma (HCC) pathogenesis requires elucidation.
Purpose of the Study:
- To investigate the expression and function of KNTC1 in HCC development.
- To explore the underlying molecular mechanisms of KNTC1's action in HCC.
- To evaluate KNTC1 as a potential therapeutic target for HCC.
Main Methods:
- Immunohistochemistry was used to assess KNTC1 expression in HCC tissues.
- Lentivirus-mediated shRNA (Lv-shKNTC1) was employed to silence KNTC1 in HCC cell lines (BEL-7404, SK-HEP-1).
- In vitro assays (proliferation, apoptosis, migration) and in vivo xenograft models were utilized to evaluate HCC progression. Western blotting assessed protein levels involved in signaling pathways.
Main Results:
- KNTC1 was highly expressed in HCC tissues and associated with poor prognosis.
- Silencing KNTC1 in HCC cells reduced proliferation, increased apoptosis, and decreased migration.
- In vivo, KNTC1 silencing significantly slowed xenograft tumor growth.
- KNTC1 knockdown led to downregulation of PIK3CA, p-Akt, CCND1, and CDK6, implicating the PI3K/Akt pathway.
- ZW10 was identified as a key mediator in KNTC1's regulation of the PI3K/Akt pathway.
Conclusions:
- KNTC1 plays a significant role in promoting HCC progression.
- The PI3K/Akt signaling pathway is a key mechanism through which KNTC1 affects HCC biological activity.
- KNTC1 represents a promising novel target for adjuvant therapy in hepatocellular carcinoma.
More Related Videos
09:24Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Related Concept Videos
Inhibition of Cdk Activity
PI3K/mTOR/AKT Signaling Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades
The JAK-STAT Signaling Pathway