Background: 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. Here, we sought to identify the biological significances of KNTC1 in hepatocellular carcinoma (HCC).
Methods: KNTC1 expression was studied in HCC tissues by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was performed to generate KNTC1 knockdown HCC cell lines. The effects of KNTC1 on HCC cells proliferation, migration, apoptosis and tumor formation was analyzed by MTT assay, colony formation assay, wound‐healing assay, transwell migration assay, annexin V assay in vitro and in nude mouse models in vivo.
Results: Our immunohistochemistry experiment showed that KNTC1 was highly expressed in HCC tissues and correlated with terrible prognosis, indicating that KNTC1 acts a pivotal role in HCC development. Furthermore, 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 SK‐HEP‐1 cells. Therefore, KNTC1 may affect the biological activity of HCC cells through PI3K/Akt signaling pathway.
Conclusions: 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.