Further investigation revealed that SUMOylation enhanced the stability of Oct-1, a transcription activator of ALDH1A1, which functioned in retinoic acid cell signaling. found that the level of SUMO E1 was higher in colorectal cancer than in corresponding normal tissues. reported that SAE1 enhanced glioma growth by increasing SUMOylation and phosphorylation at Ser473 of Akt. For instance, SUMO-1-modified MAFB promoted colorectal cancer tumorigenesis via cell cycle regulation. Recent studies found that the dysregulation of SUMOylation contributed to the initiation and development of cancer, and that most SUMO-related genes, including SUMO-2 and SUMO-activating enzyme subunit 1 (SAE1), were overexpressed in many types of tumor. SUMO-4 is usually nonconjugated under normal conditions. SUMO-2 and SUMO-3 share 95% homology with each other, but they are only 45% identical to SUMO-1. SUMO-1 usually modifies substrates as a monomer, while SUMO-2/3 can form poly-SUMO chains. In mammalian cells, the SUMO family consists of four isoforms (SUMO1–4). The modification changes the molecular surface of target proteins, which may affect protein–protein interactions, activity, stability, or cellular localization of substrates. Three enzymatic steps occur during SUMOylation: SUMO activation catalyzed by SUMO-activating enzyme E1, SUMO conjugation to conjugating enzyme E2 (Ubc9), and SUMO conjugation to substrate catalyzed by E2 and SUMO ligases E3. Accumulating evidence suggest that SUMOylation participates in many cellular activities, such as transcription regulation, DNA repair, signal transduction, protein degradation, and so forth. SUMOylation is a well-recognized post-translational modification (PTM) during which a small ubiquitin-like modifier (SUMO) protein is conjugated to lysine residues of target proteins. These pieces of evidence suggested that the regulatory mechanism of the cell cycle in HCC still remained unclear. reported that ribociclib and abemaciclib, two CDK4/6 inhibitors, had minimal effects on HCC cell viability, and palbociclib, another CDK4/6 inhibitor, exerted a cytotoxic effect on HCC in a CDK4/6-independent way. Early studies have shown that chemotherapies bring minimal benefit to patients with advanced-stage hepatocellular carcinoma (HCC). However, not all types of cancer respond well to these strategies. CDK4/6 inhibitors, in combination with endocrine therapy, lead to significantly longer overall survival (OS) compared with endocrine therapy alone in patients with advanced-stage breast cancer. For example, nucleoside analogues, which disturb DNA replication, have been in clinical use for decades and have become the cornerstone of chemotherapies. Many anticancer therapies are designed to target the aberrantly activated cell cycle and DNA replication. Uncontrolled cell proliferation is an important hallmark of cancer. SRRS could serve as an independent prognostic factor and predict the efficiency of transarterial chemoembolization in patients with HCC. Eventually, an SAE1-related risk score (SRRS) was developed and validated in HCC. IGF2BP3 contributed to the upregulation of SAE1 in an N6-methyladenosine (m6A)-dependent way. The downregulation of SAE1 inhibited the proliferation of HCC cells, whereas the upregulation of the gene promoted cell proliferation. The enrichment analysis indicated that SUMO-2 and SAE1 might regulate the cell cycle. SUMO-2 and SUMO-activating enzyme subunit 1 (SAE1) were upregulated in HCC. The least absolute shrinkage and selection operator Cox regression analysis was used to construct a prognostic model. A set of bioinformatics tools and experiments were integrated to explore the mechanism of the genes of interest. This study aimed to analyze the expression profile and prognostic relevance of SUMO-related genes using publicly available data. The function of small ubiquitin-like modifier (SUMO)-related genes in hepatocellular carcinoma (HCC) remains unclear.
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