Functional characterization of FBXL7 as a novel player in human cancers

Abstract

F-box and leucine-rich repeat protein 7 (FBXL7), an F-box protein responsible for substrate recognition by the SKP1-Cullin-1-F-box (SCF) ubiquitin ligases, plays an emerging role in the regulation of tumorigenesis and tumor progression. FBXL7 promotes polyubiquitylation and degradation of diverse substrates and is involved in many biological processes, including apoptosis, cell proliferation, cell migration and invasion, tumor metastasis, DNA damage, glucose metabolism, planar cell polarity, and drug resistance. In this review, we summarize the downstream substrates and upstream regulators of FBXL7. We then discuss its role in tumorigenesis and tumor progression as either an oncoprotein or a tumor suppressor, and further describe its aberrant expression and association with patient survival in human cancers. Finally, we provide future perspectives on validating FBXL7 as a cancer biomarker for diagnosis and prognosis and/or as a potential therapeutic target for anticancer treatment.

Establishment of a circRNA-regulated E3 ubiquitin ligase signature and nomogram to predict immunotherapeutic efficacy and prognosis in hepatocellular carcinoma

“…In addition, F-box and leucine-rich repeat protein 7 (FBXL7), an F-box protein that is accountable for substrate recognition in the SKP1-Cullin-1-F-box (SCF) ubiquitin ligases, assumes a growing function in the control of tumorigenesis and tumor progression. FBXL7 induces polyubiquitylation and breakdown of various substrates and is involved in numerous biological processes, including apoptosis, cell proliferation, cell migration and invasion, tumor metastasis, DNA damage, glucose metabolism, planar cell polarity, and drug resistance [ 55 ]. FBXL7 exhibits aberrant expression in a variety of cancers.…”

“…Patients who exhibited elevated levels of FBXL7 were found to demonstrate poorer OS across multiple cancer types, including colon adenocarcinoma, rectum adenocarcinoma, stomach cancer, liver cancer, thyroid cancer, lung cancer, and urothelial cancer. However, better survival outcomes were observed in kidney renal clear cell carcinoma, which suggests the oncogenic nature of FBXL7 [ 55 ]. WD repeat and high-mobility group box DNA-binding protein 1 (WDHD1), also recognized as acidic nucleoplasmic DNA-binding protein 1 (AND-1), and human chromosome transmission fidelity factor 4 (CTF4), is a relatively evolutionarily conserved protein with 1129 amino acids and homologs in most eukaryotes [ 56 ].…”

Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma

“…Previous studies have identified that ATG10 was associated with autophagy, immune response, and tumor metastasis in HCC ( Zhang J. et al, 2021 ; Chen et al, 2021 ; Xu et al, 2021 ), which suggested that UPS-related genes might contribute to HCC development through regulating biological process. FBXL7, an F-box protein that binds to substrates via SKP1-Cullin-1-F-box (SCF) E3 ubiquitin ligase, could enhance polyubiquitylation and degradation of substrates in tumor occurrence and aggression ( Wang et al, 2022 ). Additionally, FBXL7 reduces chemotherapy resistance by promoting the ubiquitination and degradation of survivin ( Dong et al, 2022 ).…”

The mammalian preimplantation embryo: Its role in the environmental programming of postnatal health and performance

“…For example, the addition of melatonin during IVEC prevented the development of blood pressure (Rexhaj et al, 2015) and glucose intolerance (Jia et al, 2022) observed in mice produced via IVEP. The latter effect was associated with restored hepatic expression of Fbxl7, a gene with important roles in apoptosis, cell proliferation, mitochondrial function, cancer development and protection against glucoseinduced cell injury (Ni et al, 2021;Wang et al, 2022b). The use of reproductive (i.e., from the oviduct and uterus) fluids during IVEC seems to be able to promote DNA methylation changes in in vitro-derived porcine blastocysts similar to in vivo counterparts (Canovas et al, 2017), leading to the production of pigs with physiological profiles partially resembling those of AI controls during postnatal development (París-Oller et al, 2022).…”