Silencing of KNTC1 inhibits hepatocellular carcinoma cells progression via suppressing PI3K/Akt pathway

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.

Keywords: Apoptosis; Hepatocellular carcinoma; KNTC1; PI3K/Akt; Proliferation; ZW10.