BNIPL‑2 expression is correlated with the prognosis and regulates the proliferation of colorectal cancer through CD44

Gao, Lei; Liu, Hansong; Yin, Ningwei; Zuo, Shanshan; Jin, Guangli; Hu, Yang-Xi; Hu, Desheng; Liu, Ying; Song, Qibin; Fei, Xuejie

doi:10.3892/mmr.2019.10633

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…This significantly reduced cell proliferation in both cell lines (Figure 5 C) but impacted differently in terms of invasion, potentiating 5637 and decreasing the number of T24 invasive cells (Figure 5 D). These are novel findings linking CD44 to cell proliferation in BC, supporting previous observations for breast 63 and colorectal 64 cancers, and suggesting that intense splicing of extracellular domains may play a key role in driving invasion, in agreement with observations from patient samples. Since the percentage of CD44s is significantly higher in CD44-dependent invasive cells (75% in T24 vs 5% in 5637; Figure 3 D and S4) and significantly associated with invasion (Figure 1 A-B), we also concluded that this isoform maybe used to specifically target more aggressive cancer cells subpopulations.…”

Section: Methodssupporting

confidence: 90%

Glycoproteogenomics characterizes the CD44 splicing code associated with bladder cancer invasion

Gaiteiro¹,

Soares²,

Relvas-Santos³

et al. 2022

Theranostics

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Rationale: Bladder cancer (BC) management demands the introduction of novel molecular targets for precision medicine. Cell surface glycoprotein CD44 has been widely studied as a potential biomarker of BC aggressiveness and cancer stem cells. However, significant alternative splicing and multiple glycosylation generate a myriad of glycoproteoforms with potentially distinct functional roles. The lack of tools for precise molecular characterization has led to conflicting results, delaying clinical applications. Addressing these limitations, we have interrogated the transcriptome and glycoproteome of a large BC patient cohort for splicing signatures. Methods: CD44 gene and its splicing variants were assessed by Real Time-Polymerase Chain Reaction (RT-PCR) and RNAseq in tumor tissues. The co-localization of CD44 and short O -glycans was evaluated by proximity ligation assay (PLA), immunohistochemistry and double-immunofluorescence. An innovative glycoproteogenomics approach, integrating transcriptomics-customized datasets and glycomics for protein annotation from nanoLC-ESI-MS/MS experiments, was developed and implemented to identify CD44 variants and associated glycosignatures. The impact of CD44 silencing on proliferation and invasion of BC cell lines and glycoengineered cells was determined by BrdU ELISA and Matrigel invasion assays, respectively. Antibody phosphoarrays were used to investigate the role of CD44 and its glycoforms in the activation of relevant oncogenic signaling pathways. Results: Transcriptomics analysis revealed remarkable CD44 isoforms heterogeneity in bladder cancer tissues, as well as associations between short CD44 standard splicing isoform (CD44s), invasion and poor prognosis. We further demonstrated that targeting short O -glycoforms such as the Tn and sialyl-Tn antigens was key to overcome the lack of cancer specificity presented by CD44. Glycoproteogenomics allowed, for the first time, the comprehensive characterization of CD44 splicing code at the protein level. The concept was applied to invasive human BC cell lines, glycoengineered cells, and tumor tissues, enabling unequivocal CD44s identification as well as associated glycoforms. Finally, we confirmed the link between CD44 and invasion in CD44s-enriched cells in vitro by small interfering RNA (siRNA) knockdown, supporting findings from BC tissues. The key role played by short-chain O -glycans in CD44-mediated invasion was also demonstrated through glycoengineered cell models. Conclusions: Overall, CD44s emerged as biomarker of poor prognosis and CD44-Tn/ Sialyl-Tn (STn) as promising molecular signatures for targeted interventions. This study materializes the concept of glycoproteogenomics and provides a key vision to address the cancer splicing code at the protein level, which may now be expanded to better understand CD44 functional role in ...

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Section: Methodssupporting

confidence: 90%

Glycoproteogenomics characterizes the CD44 splicing code associated with bladder cancer invasion

Gaiteiro¹,

Soares²,

Relvas-Santos³

et al. 2022

Theranostics

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“…Poor prognosis induced by ERBB2 can alter the BNIPL expression, causing an anti-apoptotic phenotype [ 33 ]. In addition, overexpression of CD44 restores the cell proliferation suppressed by BNIPL‑2 and BNIPL-2, which can promote migration, invasion, and metastasis of colorectal cancer cells via CD44 [ 34 ]. In our research, overexpression of BNIPL inhibited the proliferation, migration, and invasion of LC cells.…”

Section: Discussionmentioning

confidence: 99%

BNIPL is a promising biomarker of laryngeal cancer: novel insights from bioinformatics analysis and experimental validation

Wang,

Gao,

Wen

et al. 2024

BMC Med Genomics

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Background Laryngeal cancer (LC) is a malignant tumor with high incidence and mortality. We aim to explore key genes as novel biomarkers to find potential target of LC in clinic diagnosis and treatment. Methods We retrieved GSE143224 and GSE84957 datasets from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). Hub genes were identified from protein-protein interaction networks and further determined using receiver operating characteristic curves and principal component analysis. The expression of hub gene was verified by quantitative real time polymerase chain reaction. The transfection efficiency of BCL2 interacting protein like (BNIPL) was measured by western blot. Proliferation, migration, and invasion abilities were detected by Cell Counting Kit-8, wound-healing, and transwell assays, respectively. Results Total 96 overlapping DEGs were screened out from GSE143224 and GSE84957 datasets. Six hub genes (BNIPL, KRT4, IGFBP3, MMP10, MMP3, and TGFBI) were identified from PPI network. BNIPL was selected as the target gene. The receiver operating characteristic curves of BNIPL suggested that the false positive rate was 18.5% and the true positive rate was 81.5%, showing high predictive values for LC. The expression level of BNIPL was downregulated in TU212 and TU686 cells. Additionally, overexpression of BNIPL suppressed the proliferation, migration, and invasion of TU212 and TU686 cells. Conclusion BNIPL is a novel gene signature involved in LC progression, which exerts an inhibitory effect on LC development. These findings provide a novel insight into the pathogenesis of LC.

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BNIPL‑2 expression is correlated with the prognosis and regulates the proliferation of colorectal cancer through CD44

Cited by 2 publications

References 24 publications

Glycoproteogenomics characterizes the CD44 splicing code associated with bladder cancer invasion

Glycoproteogenomics characterizes the CD44 splicing code associated with bladder cancer invasion

BNIPL is a promising biomarker of laryngeal cancer: novel insights from bioinformatics analysis and experimental validation

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