ASF1b is a novel prognostic predictor associated with cell cycle signaling pathway in gastric cancer

Abstract

Gastric cancer (GC) is one of the most common malignant tumors with poor outcomes. Identification of new therapeutic targets is urgently needed. Accumulating evidence has shown that anti-silencing function 1b (ASF1b) contributes to the progression in multiple cancer types. However, detailed mechanisms of ASF1b tumorigenesis in gastric cancer remain elusive. This study showed that ASF1b was upregulated in GC tissues and remarkably correlated with TNM stage, histological grade and poor prognosis of GC. We induced down and up-regulation of ASF1b in GC cell lines and monitored the changes in their biological behavior. Furthermore, loss of ASF1b was efficient to suppress subcutaneous xenograft tumor growth in vivo. We demonstrate that ASF1b is involved in regulation of cell cycle and PI3K/AKT/mTOR signaling through experiments and database analysis. Mechanistically, ASF1b promoted the proliferation, migration and invasion of GC cells. Taken together, this study highlights the role of ASF1b, which provided new insights into the underlying mechanism of progression and metastasis in GC for the first time.

A molecular classification of gastric cancer associated with distinct clinical outcomes and validated by an XGBoost-based prediction model

“…44 ASF1B, ORC1, and SLC22A17 have also been found to be related to the progression or metastasis of GC. 44 , 45 , 46 It has been reported that the expression levels of DKK1, MATN3, and IGFBP1 are significantly associated with survival in patients with GC. 47 , 48 , 49 In addition to CDH1, RHOA is a representative mutation driver gene for the diffuse-type and GS subtype.…”

PFN4 is required for manchette development and acrosome biogenesis during mouse spermiogenesis

“…In order to load equal amounts of protein, the concentration of supernatant was measured using the Pierce BCA Protein-Assay Kit (Thermo Fisher Scientific). SDS gel followed by western blot was performed as described previously ( Umer et al, 2021 ) with primary antibodies against LC3I/II (1:1000; ab58610, Abcam), p-mTOR (1:1000; 2971, Cell Signaling Technology), mTOR (1:1000; 2972, Cell Signaling Technology), SQSTM1 (1:1000; 5114, Cell Signaling Technology), AMPK (1:1000; 5831, Cell Signaling Technology), β-actin (1:10,000; A5441, Sigma-Aldrich), as described previously ( Umer et al, 2021 ), ARF3 (1:1000; 10800-1-AP), FKBP1 (1:1000; 10273-1-AP) ( Hou et al, 2017 ), SPECC1L (1:1000; PA5-71632; Thermo Fisher Scientific), p-AKT (1:2000; 4060, Cell Signaling Technology), p-PI3K (1:1000; 17366, Cell Signaling Technology), PI3K (1:1000; 4263, Cell Signaling Technology) and AKT (1:1000; 4691, Cell Signaling Technology), as described previously ( Chen et al, 2022 ).…”

Histone Chaperones and Digestive Cancer: A Review of the Literature

“…ASF1B is overexpressed in HCC [ 16 , 18 ] and GC [ 19 ], and is negatively correlated with their prognoses. ASF1B is associated with multiple phenotypes of digestive cancer cells, including proliferation [ 16 , 19 ], migration [ 18 ], apoptosis [ 21 ], DNA damage [ 20 ], and chemosensitivity [ 20 ]. For upstream regulatory networks, Zhan reported that the miRNA-214-3p negatively transcriptionally regulates ASF1B [ 17 ].…”

“…Ouyang believed that ASF1B stabilizes CDK9 protein by inhibiting its proteasome-mediated ubiquitination and degradation. In addition, both Wang and Chen discovered that ASF1B affects PI3K-AKT and cell proliferation [ 19 , 21 ]. However, neither study elucidated the detailed mechanism by which ASF1B regulates the PI3K/AKT pathway.…”

“…However, two studies required multivariate analysis to determine whether ASF1A overexpression is an independent predictor of poor outcome. ASF1B is an independent poor prognostic factor for HCC and GC [ 18 , 19 ]. Additionally, the in vivo tumor-promoting roles of ASF1A and ASF1B were validated via cell line-derived xenograft (CDX) models of CRC and GC, respectively.…”