INCENP (Inner Centromere Protein) is Overexpressed in High Grade Non-Hodgkin B-cell Lymphomas

Barbanis, Sotirios; Ιωάννου, Μαρία; Kouvaras, Evangelos; Karasavvidou, Foteini; Νάκου, Μαρία; Papamichali, Roidoula; Koukoulis, George Κ.

doi:10.1007/s12253-008-9094-0

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…High INCENP expression has been reported in some cancer types. In high-grade non-Hodgkin B-cell lymphomas (18), there is significantly higher nuclear IHC signal of INCENP compared with low-grade ones. High expression of three components of CPC (Aurora B, INCENP, and survivin) except Borealin is associated with poor survival rate in patients with NSCLC (19).…”

Section: Discussionmentioning

confidence: 91%

“…(GWAS) studies have identified SNPs in INCENP that are linked to increased susceptibility and risk in breast, ovarian, and prostate cancer (16,17). In addition, INCENP has been found to be overexpressed in high-grade non-Hodgkin B-cell lymphomas and non-small-cell lung cancer, and proposed to be a biomarker for poor prognosis in these types of cancer (18,19). However, the function and therapeutic potential of targeting INCENP in neuroblastoma remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Targeting the Chromosomal Passenger Complex Subunit INCENP Induces Polyploidization, Apoptosis, and Senescence in Neuroblastoma

et al. 2019

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Chromosomal passenger complex (CPC) has been demonstrated to be a potential target of cancer therapy by inhibiting Aurora B or survivin in different types of cancer including neuroblastoma. However, chemical inhibition of either Aurora B or survivin does not target CPC specifically due to off-target effects or CPC-independent activities of these two components. In a previous chromatin-focused siRNA screen, we found that neuroblastoma cells were particularly vulnerable to loss of INCENP, a gene encoding a key scaffolding component of the CPC. In this study, INCENP was highly expressed by neuroblastoma cells, and its expression decreased following retinoic acidinduced neuroblastoma differentiation. Elevated levels of INCENP were significantly associated with poor prognosis in primary tumors of neuroblastoma patients with high-risk disease. Genetic silencing of INCENP reduced the growth of both MYCN-wild-type and MYCN-amplified neuroblasto-ma cell lines in vitro and decreased the growth of neuroblastoma xenografts in vivo, with significant increases in murine survival. Mechanistically, INCENP depletion suppressed neuroblastoma cell growth by inducing polyploidization, apoptosis, and senescence. In most neuroblastoma cell lines tested in vitro, apoptosis was the primary cell fate after INCENP silencing due to induction of DNA damage response and activation of the p53-p21 axis. These results confirm that CPC is a therapeutic target in neuroblastoma, and targeting INCENP is a novel way to disrupt the activity of CPC and inhibit tumor progression in neuroblastoma.Significance: Dysregulation of INCENP contributes to neuroblastoma tumorigenesis and targeting INCENP presents a novel strategy to disrupt the activity of chromosomal passenger complex and inhibit neuroblastoma progression. INCENP encodes the inner centromere protein (INCENP), which is the structural and regulatory component of the chromosomal passenger complex (CPC) comprised of INCENP, survivin, Borealin, and the Aurora B kinase (9). CPC is responsible for proper chromosomal alignment, segregation, and cytokinesis during the mitosis (9). In the CPC, INCENP plays two critical roles: firstly, it functions as a scaffold protein coordinating assembly of this complex by interacting with all the other three components, and secondarily, the interaction between INCENP and Aurora B is necessary for activation of the Aurora B kinase, the catalytic subunit of this complex (9). Thus, disruption of INCENP expression leads to dissociation of the whole complex and limits Aurora B kinase activity (10, 11). Targeting the CPC has been led by strategies aimed at targeting survivin or Aurora B kinase in neuroblastoma because inhibition of either of them significantly blocks neuroblastoma tumor cell growth in vitro and xenograft growth in vivo (12-15). Recent genome-wide meta-analyses

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Targeting the Chromosomal Passenger Complex Subunit INCENP Induces Polyploidization, Apoptosis, and Senescence in Neuroblastoma

et al. 2019

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“…In addition, CENP-A has been associated with cancers such as breast cancer and lung adenocarcinoma (33,34). At the same time, CENP-E, CENP-F, and inner centromere protein have been demonstrated to contribute to carcinogenesis (35)(36)(37)(38). All observations suggest that deregulation of centromere proteins is common in the development and progression of various tumors.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CENP-H as a novel prognostic biomarker for human hepatocellular carcinoma progression and patient survival

Shan

et al. 2013

Oncology Reports

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Centromere protein H (CENP-H) has been shown to be significantly upregulated in many types of cancers and is associated with disrupted cell cycle regulation, cell proliferation and genetic instability. The aim of the present study was to explore the expression and localization of CENP-H in hepatocellular carcinoma (HCC) and determine whether its overexpression is a prognostic biomarker for HCC. Reverse transcription-polymerase chain reaction (pcr), real-time qPCR and western blotting were used to compare CENP-H expression at the mRNA and protein levels in HCC samples and corresponding adjacent non-cancerous samples. CENP-H protein levels were determined in 60 paired paraffin-embedded HCC tissues using immunohistochemistry (IHC), and the correlation with clinicopathological features and patient prognosis was analyzed. In addition, an immunofluorescence assay was performed to test the expression and localization of CENP-H protein in HCC cells. Results showed that levels of CENP-H mRNA and protein were higher in HCC samples than in the corresponding adjacent non-cancerous samples. In 60 paired paraffin-embedded tissues, CENP-H was upregulated in the HCC samples (38/60, 63.3%) relative to the adjacent non-cancerous samples (21/60, 35%, P=0.003), and a higher level of upregulation was associated with tumor size (P=0.032); higher histological grade (P=0.001); more advanced TNM stage (P=0.002) and Chinese clinical stage (P=0.008); and poorer prognosis. In addition, consistent with the results of IHC, the immunofluorescence assay showed that CENP-H was localized in the nucleus of Hep3B cells. CENP-H was overexpressed in HCC, and its level of upregulation was an independent prognostic indicator, suggesting that CENP-H may be an effective therapeutic strategy for the treatment of HCC.

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“…INCENP is a versatile domain protein composed of two types of peptides (135 and 155 kD) in close contact with chromosome proteins during cell division. INCENP , a part of a protein complex known as the chromosomal passenger complex (CPC), does not only play an important role in cell division [ 16 ] but is also closely related to cancer [ 17 , 18 ] and reproductive disorders [ 19 ]. Hering et al (2014) performed a genome-wide association study of high and low sperm motility of Holstein cattle to identify candidate genes associated with semen quality by screening all the genetic distances that significantly mark 1 Mb.…”

Section: Introductionmentioning

confidence: 99%

Functional SNPs of INCENP Affect Semen Quality by Alternative Splicing Mode and Binding Affinity with the Target Bta-miR-378 in Chinese Holstein Bulls

et al. 2016

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Inner centromere protein (INCENP) plays an important role in mitosis and meiosis as the main member of chromosomal passenger protein complex (CPC). To investigate the functional markers of the INCENP gene associated with semen quality, the single nucleotide polymorphisms (SNPs) g.19970 A>G and g.34078 T>G were identified and analyzed. The new splice variant INCENP-TV is characterized by the deletion of exon 12. The g.19970 A>G in the exonic splicing enhancer (ESE) motif region results in an aberrant splice variant by constructing two minigene expression vectors using the pSPL3 exon capturing vector and transfecting vectors into MLTC-1 cells. INCENP-TV was more highly expressed than INCENP-reference in adult bull testes. The g.34078 T>G located in the binding region of bta-miR-378 could affect the expression of INCENP, which was verified by luciferase assay. To analyze comprehensively the correlation of SNPs with sperm quality, haplotype combinations constructed by g.19970 A>G and g.34078 T>G, as well as g.-692 C>T and g.-556 G>T reported in our previous studies, were analyzed. The bulls with H1H12 and H2H2 exhibited a higher ejaculate volume than those with H2H10 and H9H12, respectively (P < 0.05). Bulls with H11H11 and H2H10 exhibited higher initial sperm motility than those with H2H2 (P < 0.05). The expression levels of INCENP in bulls with H1H12 and H11H11 were significantly higher than those in bulls with H9H12 (P < 0.05), as determined by qRT-PCR. Findings suggest that g.19970 A>G and g.34078 T>G in INCENP both of which appear to change the molecular and biological characteristics of the mRNA transcribed from the locus may serve as a biomarkers of male bovine fertility by affecting alternative splicing mode and binding affinity with the target bta-miR-378.

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INCENP (Inner Centromere Protein) is Overexpressed in High Grade Non-Hodgkin B-cell Lymphomas

Cited by 7 publications

References 26 publications

Targeting the Chromosomal Passenger Complex Subunit INCENP Induces Polyploidization, Apoptosis, and Senescence in Neuroblastoma

Targeting the Chromosomal Passenger Complex Subunit INCENP Induces Polyploidization, Apoptosis, and Senescence in Neuroblastoma

Overexpression of CENP-H as a novel prognostic biomarker for human hepatocellular carcinoma progression and patient survival

Functional SNPs of INCENP Affect Semen Quality by Alternative Splicing Mode and Binding Affinity with the Target Bta-miR-378 in Chinese Holstein Bulls

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