CDC20 regulates the cell proliferation and radiosensitivity of P53 mutant HCC cells through the Bcl-2/Bax pathway

Abstract

Purpose: The incidence of hepatocellular carcinoma (HCC) is extremely high, and China accounts for approximately 50% of global liver cancer cases. Previous studies reported that CDC20 is involved in the occurrence and progression of a variety of malignant tumors. So, whether CDC20 will affect the development of HCC, we have conducted in-depth research on this. Methods: We selected Hep3B and HepG2 for cell culture, and performed siRNA transfection, lentiviral infection, western blot, MTS determination, cell cycle determination, apoptosis test, immunodeficiency test, clone survival test and subcutaneous parthenogenesis in nude mice. Results: Knockdown of CDC20 greatly enhanced the radiation efficacy on the growth retardation in HepG2, and protein level of CDC20 was decreased for the activation of P53 by radiation. Downregulation of CDC20 combined with radiation can inhibit proliferation, aggravate DNA damage, increase G2/M arrest, and promote apoptosis of HCC cells to a greater extent, and the relative survival fraction of HCC cells was gradually reduced with radiation dose increased in P53 mutated Hep3B cells. After knocking down CDC20 in HCC, Bcl-2 was down-regulated and Bax expression increased. Down-regulation of CDC20 can inhibit further invasion by promoting the radiosensitivity of HCC. Conclusion: In this study, we found that that CDC20 was highly expressed in HCC and participated in radio resistance of HCC cells with P53 mutation Bcl-2/Bax via signaling pathway. This study is the first to present evidence that CDC20 may play a role in improving the efficacy of radiotherapy in HCC.

A Novel Gene Signature Based on CDC20 and FCN3 for Prediction of Prognosis and Immune Features in Patients with Hepatocellular Carcinoma

“…For instance, CDC20 was reported to be highly increased and served as an unfavorable prognosis marker in HCC samples. Knockdown of CDC20 noticeably promoted the radiation efficacies on the growth retardation in HCC cells via regulating Bcl-2/Bax signal, and the expressions of CDC20 were noticeably reduced due to the overexpression of P53 through radiation [ 26 ]. Yu et al reported that E2F1, which was highly expressed in HCC, mediated DDX11 transcriptional activation facilitates HCC cells' invasion, migration, and proliferation via PI3K/AKT/mTOR pathway [ 27 ].…”

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

“…CDC20 has been also involved in the apoptotic response, by regulating phosphatidylcholine (PC) cycle [ 102 , 103 ] and balancing the activity of anti-apoptotic factors, as MCL-1 [ 104 – 108 ] and BCL-2 [ 108 , 109 ], and pro-apoptotic factors, as BIM [ 110 ] (Fig. 5 A-D).…”

Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic

“…CDC20 is overexpressed in tumor cells and acts as a poor prognostic factor in multiple cancers (63,64). It further increased after radiation and has been reported to increase radiation resistance via regulating B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax), forkhead box proteins O1 (FoxO1), or myeloid cell leukemia sequence 1 (Mcl-1)/p-CHK1 in different cancer types (65)(66)(67). Suppression of CDC20 expression reverses the radioresistance (65)(66)(67).…”