Silencing CDC25A inhibits the proliferation of liver cancer cells by downregulating IL‑6 in�vitro and in�vivo

Abstract

cell division cycle 25A (cdc25A) is a core regulator of the cell cycle that has a dual-specific phosphatase activity, which is closely associated with the occurrence and development of a tumor, and is overexpressed in liver cancer. However, the molecular mechanism of cdc25A in the development of liver cancer remains unclear. The purpose of the present study was to further investigate the effect of cdc25A on cell proliferation in vitro and in vivo and to investigate whether an interaction exists between cdc25A and interleukin (IL)-6 in liver cancer. An Affymetrix human gene expression profiling chip screened differentially expressed genes in HepG2 cells with silenced cdc25A and the IL-6 signaling pathway was revealed to be significantly inhibited (P<0.05). In the present study, the effects of cdc25A on cell proliferation and migration were analyzed using cell cycle, MTT and Transwell assays. Reverse transcription-quantitative PCR, western blot and immunohistochemistry analyses confirmed that silencing the cdc25A gene downregulated the expression of IL-6 in HepG2 cells and the mRNA and protein expression of IL-1β, mitogen-activated protein kinase kinase kinase 14 (NIK) and nuclear factor-κB (NF-κB), which are regulatory molecules upstream of IL-6. In addition, silencing cdc25A by short hairpin RNA inhibited the development of liver cancer xenograft tumor types in nude mice, and decreased the expression of IL-1β, NIK, NF-κB and IL-6 in xenograft tumor types. In conclusion, silencing CDC25A significantly inhibited the proliferation of liver cancer cells in vitro and in vivo, potentially via an interaction with IL-6 through the downregulation of the IL-1β/NIK/NF-κB signaling axis.

The LINC00261/MiR105-5p/SELL axis is involved in dysfunction of B cell and is associated with overall survival in hepatocellular carcinoma

“…The up-regulation of REPS2 is associated with nuclear DKK-1 expression and is correlated with decreased OS in colorectal cancer ( Aguilera et al, 2015 ). Silencing CDC25A significantly inhibits the proliferation of liver cancer cells in vitro and in vivo ( Chen et al, 2020 ). The overexpression of GPR19 can regulate E-cadherin expression and invasion of breast cancer cells ( Rao & Herr, 2017 ).…”

Comprehensive bioinformatics analysis for MEF2 family genes in gastric cancer

“…Six miRNAs ( miRNA-7-1, miRNA-17, miRNA-183, miRNA-210, miRNA-219a-1, and miRNA-942 ) and 5 miRNA modulators ( CDC25A , CDCA5 , E2F1 , EZH2 , and KIF23 ) were found to be significantly correlated with MEF2 expression and have a prognostic impact on GC patients. CDC25A is a member of the cell division cycle 25 family, which has been reported to be overexpressed in a wide range of cancer types and associated with cancer cell survival and tumor growth ( 31 - 34 ). Unlike some previous studies ( 35 - 37 ), we found that overexpression of CDC25A could prolong GC survival.…”

Long Noncoding RNA Expression Rofiles Elucidate the Potential Roles of lncRNA- XR_003496198 in Duck Hepatitis A Virus Type 1 Infection

“…Cytokines are soluble extracellular mediators such as chemokines, IFN, interleukins (IL), lymphokines, and tumor necrosis factors, which have important roles in immune response activation. IL-6 is a pleiotropic cytokine that regulates hematopoiesis and immune and inflammatory responses and contributes to T and B cell activation, proliferation, and differentiation (Chen et al, 2020). IL-8, also known as CXCL8, is an important immune response mediator produced by macrophages and peripheral blood mononuclear cells (Zou et al, 2016).…”