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.

Cellular Signalling
|October 23, 2022
PubMed

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.

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