HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis

Chen, Er‐Bao; Qin, Xuan; Peng, Ke; Li, Qian; Tang, Cheng; Wei, Yimin; Yu, Shan; Gan, Lu; Liu, Tianshu

doi:10.18632/aging.102254

Cited by 87 publications

(66 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, there is no reported functional role of CENPF implicated in CC. However, CENPF was reported to be overexpressed, drive tumorigenesis and/or associated with poor prognosis in several human malignancies, including breast cancer [40], prostate cancer [41][42][43][44], bladder cancer [45], gastric cancer [46], hepatocellular carcinoma [47][48][49], pancreatic carcinoma [50]. In this study, higher CENPF expression was found to be significantly associated with metastasis compared to CC tissues (Fig.…”

Section: Discussionmentioning

confidence: 49%

“…Small molecule compounds targeting CENPF have not been reported, possibly attributed by the difficulty to target a non-enzyme target. However, reports have shown that silencing CENPF using in vitro models abolished invasion in gastric cancer [46], resulted in the cell cycle arrest at G2/M checkpoint in hepatocellular carcinoma [47], reduced levels of epithelialmesenchymal transition markers, inhibited cell proliferation, migration, and invasion, reduced global bioenergetic capacity and altered the global metabolic profiles in prostate cancer [43,53]. It remained to be validated whether silencing/inhibiting either CENPF or both CENPF and TOP2A will have a strong phenotypic consequence in CC using an in-vitro or/and in vivo model.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TOP2A and CENPF are synergistic master regulators activated in cervical cancer

Yu¹,

Chen

Zhang

et al. 2020

BMC Med Genomics

View full text Add to dashboard Cite

Background Identification of master regulators (MRs) using transcriptome data in cervical cancer (CC) could help us to develop biomarkers and find novel drug targets to fight this disease. Methods We performed differential expression (DE) analyses of public microarray and RNA-seq transcriptome data of CC and normal cervical tissues (N). Virtual Inference of Protein activity by Enriched Regulon analysis (VIPER) was used to convert the DE outcomes to differential activity (DA) signature for MRs. Synergy analysis was conducted to study synergistic effect of MR-pairs. TCGA and microarray data were used to test the association of expression of a MR and a clinical feature or a molecular feature (e.g. somatic mutations). Various bioinformatic tools/websites (DAVID, GEPIA2, Oncomine, cBioPortal) were used to analyze the expression of the top MRs and their regulons. Results Ten DE and 10 DA signatures were generated for CC. Two MRs, DNA topoisomerase II alpha (TOP2A) and centromere protein F (CENPF) were found to be up-regulated, activated and synergistic in CC compared to N across the 10 datasets. The two MRs activate a common set of genes (regulons) with functions in cell cycle, chromosome, DNA damage etc. Higher expression of CENPF was associated with metastasis. High expression of both MRs is associated with somatic mutation of a set of genes including tumor suppressors (TP53, MSH2, RB1) and genes involved in cancer pathways, cell cycle, DNA damage and repair. The magnitude of up-regulation and the absolute expression level of both MRs in CC are significantly higher compared to many other cancer types. Conclusion TOP2A and CENPF are a synergistic pair of MRs that are overexpressed and activated in CC. Their high expression is correlated with some prognosis features (e.g. metastasis) and molecular features (e.g. somatic mutations) and distinctly high in CC vs. many other cancer types. They may be good biomarkers and anticancer drug targets for CC.

show abstract

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

TOP2A and CENPF are synergistic master regulators activated in cervical cancer

Yu¹,

Chen

Zhang

et al. 2020

BMC Med Genomics

View full text Add to dashboard Cite

show abstract

“…According to previous studies, MCM3AP-AS1 could hasten tumor growth in breast cancer by targeting CENPF via competitively binding to miR-28-5p 17 . Besides, overexpression of hnRNPR promoted the aggressiveness of gastric cancer by increasing the mRNA expression of CCNB1 and CENPF 18 . Maybe the molecular mechanisms underlying the effects of CENPF on the oncogenesis of LUAD also could be regulated by noncoding RNAs.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma

Li¹,

Zhang²,

Dong³

et al. 2021

Int. J. Med. Sci.

View full text Add to dashboard Cite

Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. Methods: CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. Results: CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) ( P < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.

show abstract

“…However, not all patients could benefit from anti-HER2 or anti-VEGFR monoclonal antibody and the monoclonal antibodies are not suitable for GC patients with negative HER2 or VEGFR expression [12]. Therefore, it is imperative to further elucidate the molecular mechanisms underlying GC invasion and metastasis fully so as to identify novel effective therapeutic targets [13].…”

Section: Introductionmentioning

confidence: 99%

LDLRAD2 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in gastric cancer

Wei

Zhang

et al. 2019

Aging

View full text Add to dashboard Cite

The therapeutic strategies for advanced gastric cancer (GC) remain unsatisfying and limited. Therefore, it is still imperative to fully elucidate the mechanisms underlying GC aggressive progression. The prognostic value and biological functions of low density lipoprotein receptor class A domain containing protein 2 (LDLRAD2) in GC have never been studied yet. We found that LDLRAD2 expression was significantly upregulated in GC and closely correlated with poor prognosis in GC patients. Functionally, LDLRAD2 promoted epithelial-mesenchymal transition, migration and invasion, and metastasis of GC cells. Mechanistically, LDLRAD2 interacted with and inhibited Axin1 from binding to cytoplasmic β-catenin, which facilitated the nuclear translocation of β-catenin, thereby activating Wnt/β-catenin pathway. Inhibition of β-catenin activity markedly abolished LDLRAD2-induced migration, invasion and metastasis. Together, these results suggested that LDLRAD2 contributed to invasion and metastasis of GC through activating Wnt/β-catenin pathway. LDLRAD2/ Wnt/β-catenin axis may be a potential therapeutic target for GC treatment.

show abstract

HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis

Cited by 87 publications

References 41 publications

TOP2A and CENPF are synergistic master regulators activated in cervical cancer

TOP2A and CENPF are synergistic master regulators activated in cervical cancer

Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma

LDLRAD2 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in gastric cancer

Contact Info

Product

Resources

About