<i>FBXW7</i>Mutations Promote Cell Proliferation, Migration, and Invasion in Cervical Cancer

Liu, Faying; Zou, Yang; Wang, Feng; Yang, Bicheng; Zhang, Ziyu; Luo, Yong; Liang, Meirong; Zhou, Jiangyan; Huang, Ouping

doi:10.1089/gtmb.2018.0278

Cited by 17 publications

(14 citation statements)

References 35 publications

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“…Cheng et al [ 48 ] found that FBXW7 inhibited the migration and invasion in melanoma cells. Moreover, FBXW7 mutation could be able to promote cell migration and invasion of CC cells [ 49 ]. Interestingly, FBXW7 has recently been studied as a target gene of miRNAs in various cancers.…”

Section: Discussionmentioning

confidence: 99%

The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

et al. 2022

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MicroRNAs (miRNAs) have been reported to be involved in the initiation and progression of human tumors including cervical cancer (CC). However, the mechanisms underlying of their actions in CC remain to be fully elucidated. Herein, the differentially expressed miRNAs that were screened based on GSE55940 microarray data retrieved from Gene Expression Omnibus (GEO), and miR-103a-3p was significantly upregulated in CC tissues which was selected as the target miRNA for further research. We also found that high expression of miR-103a-3p was closely associated with histological grades, FIGO stage and distant metastasis as well as reflected poor overall survival. Moreover, miR-103a-3p inhibition decreased the growth capacity of SiHa and HeLa cells by inducing cell apoptosis. And F-box and WD repeat-domain containing protein 7 (FBXW7), a well-known tumor suppressor in many cancer types, was identified as a direct target of miR-103a-3p. It was further found that FBXW7 was significantly downregulated in CC tissues, and it was inversely correlated with miR-103a-3p expression levels. Further investigation demonstrated that FBXW7 upregulation could simulate the roles of miR-103a-3p knockdown in cell viability and apoptosis. Moreover, FBXW7 knockdown efficiently abrogated the influences of CC cells proliferation caused by miR-103a-3p inhibition. Notably, miR-103a-3p could block FBXW7 mediated the downstream transcription factor pathways. Taken together, these findings suggest that miR-103a-3p functions as an oncogene in CC by targeting FBXW7.

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Section: Discussionmentioning

confidence: 99%

The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

et al. 2022

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“…With the application and development of high‐throughput sequencing, gene chip in research of tumor genomics, it is significant to find the mechanism, prognostic factors, and potential therapeutic targets of cervical cancer. Some studies have reported that mutations of FOXP3 (Cezar‐Dos‐Santos et al, 2019), PIK3CA (Razia et al, 2019), XRCC4 (Gupta, Kushwah, Singh, & Banerjee, 2019), FBXW7 (Liu et al, 2019), and some copy number variations of KLF10 and PSG (Marrero‐Rodriguez et al, 2018) are related to the carcinogenesis and pathogenesis of cervical cancer, but they were not complete so that to be further studied. This study aim to better understand the characteristics of some genes and signaling pathways that associate with cervical cancer through bioinformatics.…”

Section: Introductionmentioning

confidence: 99%

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Yang

Xue

et al. 2020

Molec Gen & Gen Med

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Background Cervical cancer as one of the most common malignant tumors lead to bad prognosis among women. Some researches already focus on the carcinogenesis and pathogenesis of cervical cancer, but it is still necessary to identify more key genes and pathways. Methods Differentially expressed genes were identified by GEO2R from the gene expression omnibus (GEO) website, then gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyzed by DAVID. Meanwhile, protein–protein interaction network was constructed by STRING, and both key genes and modules were found in visualizing network through Cytoscape. Besides, GEPIA did the differential expression of key genes and survival analysis. Finally, the expression of genes related to prognosis was further explored by UNLCAN, oncomine, and the human protein atlas. Results Totally 57 differentially expressed genes were founded, not only enriched in G1/S transition of mitotic cell cycle, mitotic nuclear division, and cell division but also participated in cytokine–cytokine receptor interaction, toll‐like receptor signaling pathway, and amoebiasis. Additionally, 12 hub genes and 3 key modules were screened in the Cytoscape visualization network. Further survival analysis showed that TYMS (OMIM accession number ), MCM2 (OMIM accession number ), HELLS (OMIM accession number ), TOP2A (OMIM accession number ), and CXCL8 (OMIM accession number ) were associated with the prognosis of cervical cancer. Conclusion This study aim to better understand the characteristics of some genes and signaling pathways about cervical cancer by bioinformatics, and could provide further research ideas to find new mechanism, more prognostic factors, and potential therapeutic targets for cervical cancer.

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“…In R465C mice, Fbxw7 protein function is lost, as indicated by a lack of Fbxw7-substrate interaction and poor substrate degradation by Fbxw7, resulting in prolonged Notch1 intracellular domain and Myc expression [46], as well as decreased degradation of Klf5 [49]. In culture, aberrant subnuclear localization resulted in lower inhibition of migration, invasion, and colony formation compared to wild-type Fbxw7 [48,50]. The WD repeat 3 of the Fbxw7 protein contains R465H (which corresponds to R385H in isoform 2.…”

Section: Structural Effect Of Point Mutation On Human Fbxw7 Proteinmentioning

confidence: 99%

“…The tumour suppressor FBXW7 is typically mutated in serous ECs compared with other clinically aggressive subtypes [8,12]. Nearly 15%-29% of serous ECs, 11-39% of uterine carcinosarcomas, 13-25% of clear cell endometrial cancers, and 0%-15% of endometrioid endometrial cancers were reported with somatic mutations in FBXW7 [10,11]. As a result, it has been hypothesized that reduced expression or deletion of FBXW7 in breast cancer leads to an accumulation of oncogenic transcription factors, which are key regulators of proliferation, apoptosis, and eventually transformation [13].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Study of Human FBXW7 Deleterious nsSNP’s Functional Inference and Susceptibility to Gynaecological Cancer

Vasuki

Christy

2021

Appl Biochem Biotechnol

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Cancer is one of the world's major causes of mortality, and it plays a most important role in the world's declining life expectancy. F-box and WD-40 domain protein 7 (FBXW7), a typical participant of the F-box family of proteins, has been considered as an antitumor protein and one of the maximum deregulated ubiquitin-proteasome system proteins in uterine carcinosarcoma, endometrial clear cell carcinoma and cervical carcinoma with the greatest prevalence of alterations. FBXW7 variants with known clinical signi cance, as well as nsSNP's in the F-Box and WD40 domains, were evaluated using functionality prediction web resources. Upon analysing the seventy-three deleterious nsSNP's impact on protein stability and function, we identi ed that forty-one nsSNP's of WD40 domain and three of F-Box domain imply decreased stability of the FBXW7 structure. Next to TP53 and PTEN, FBXW7 was reported with the highest percentage of arginine substitution among mutations related to cancer. The current research concentrated on two arginine residue locations (Arg465, Arg505) within the WD40-repeat domain, which is vital for substrate binding. Computational analysis revealed that signi cant deviation in stability and structural con guration of mutants R505L, R465H, R465P, R505G, R505C, R465C R505S and R505L structures. Proteinprotein interaction network of FBXW7 populated with promising hub proteins NOTCH1, c-Myc, CCNE1, STYX, KLG5, SREB1, NFKB2, SKP1, CUL1, thus alteration in the FBXW7 leads to aberration in their signalling pathways as well as their substrate binding ability makes this protein as attractive target for personalized therapeutic intervention.

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FBXW7Mutations Promote Cell Proliferation, Migration, and Invasion in Cervical Cancer

Cited by 17 publications

References 35 publications

The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

The promotional effect of microRNA-103a-3p in cervical cancer cells by regulating the ubiquitin ligase FBXW7 function

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Comprehensive Study of Human FBXW7 Deleterious nsSNP’s Functional Inference and Susceptibility to Gynaecological Cancer

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