Enhanced expression of cohesin loading factor NIPBL confers poor prognosis and chemotherapy resistance in non-small cell lung cancer

Xu, Weizhen; Ying, Yinyin; Shan, Lihong; Jiang, Feng; Zhang, Shengjie; Gao, Yun; Xu, Xiaoling; Yao, Yinli; Zhu, Chihong; Mao, Weimin

doi:10.1186/s12967-015-0503-3

Cited by 29 publications

(20 citation statements)

References 42 publications

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“…The relationship between CDRC expression pattern and clinicopathologic parameters was evaluated. The results indicated that increased DNA repair capacity was correlated with poor tumor differentiation and poor survival 29 30 , which was also validated in the independent cohort. However, interestingly, intrinsic HCC subtypes by CDRC were not contingent on tumour stage or other single clinicopathologic parameter.…”

Section: Discussionsupporting

confidence: 56%

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

Lin

Wang

et al. 2016

Sci Rep

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Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy.

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Section: Discussionsupporting

confidence: 56%

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

Lin

Wang

et al. 2016

Sci Rep

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“…For example, Xu et al 51 showed that enhanced RAD21 expression confers poor prognosis and drug resistance in high grade luminal, basal and HER2+ breast cancers, while Deb and colleagues 52 showed that RAD21 overexpression is predictive of poor prognosis in KRAS mutant colorectal cancers. In addition, enhanced NIPBL expression is associated with poor prognosis and chemotherapy resistance in non-small cell lung cancer 53 , while SMC1A overexpression contributes to colorectal cancer development in a mouse model 54 . While speculative, these findings, coupled with data from the current study strongly suggest that cohesion gene expression is normally tightly regulated, and that deviations, either through gene copy number losses or gains, may be etiological events contributing to the development and progression of cancer, although this remains to be empirically determined.…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of Genes Regulating Cohesion Induces Chromosome Instability that May Promote Cancer and Impact Patient Outcomes

Leylek

Jeusset

Lichtensztejn

et al. 2020

Sci Rep

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chromosome instability (cin), or continual changes in chromosome complements, is an enabling feature of cancer; however, the molecular determinants of cin remain largely unknown. emerging data now suggest that aberrant sister chromatid cohesion may induce cin and contribute to cancer. to explore this possibility, we employed clinical and fundamental approaches to systematically assess the impact reduced cohesion gene expression has on cin and cancer. ten genes encoding critical functions in cohesion were evaluated and remarkably, each exhibits copy number losses in 12 common cancer types, and reduced expression is associated with worse patient survival. to gain mechanistic insight, we combined siRnA-based silencing with single cell quantitative imaging microscopy to comprehensively assess the impact reduced expression has on cin in two karyotypically stable cell lines. We show that reduced expression induces cin phenotypes, namely increases in micronucleus formation and nuclear areas. Subsequent direct tests involving a subset of prioritized genes also revealed significant changes in chromosome numbers with corresponding increases in moderate and severe cohesion defects within mitotic chromosome spreads. Collectively, our clinical and fundamental findings implicate reduced sister chromatid cohesion, resulting from gene copy number losses, as a key pathogenic event in the development and progression of many cancer types.

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“…Another molecule that is strongly predicted to be a target of miR-410 is NIPBL. NIPBL (Nipped-B-like protein), also known as delangin or SCC2 homolog is a marker for poor prognosis and promotes chemotherapy resistance ( 46 ). As we have previously discussed, metastatic neuroblastomas show little to no expression of SPARC and SPARC overexpression is known to induce expression of miR-410 by a yet unknown mechanism.…”

Section: Discussionmentioning

confidence: 99%

SPARC overexpression combined with radiation retards angiogenesis by suppressing VEGF-A via miR-410 in human neuroblastoma cells

Boyineni

Tanpure

Gnanamony

et al. 2016

International Journal of Oncology

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Neuroblastoma (NB) is the most common extracranial solid tumor in children and despite aggressive therapy survival rates remain low. One of the contributing factors for low survival rates is aggressive tumor angiogenesis, which is known to increase due to radiation, one of the standard therapies for neuroblastoma. Therefore, targeting tumor angiogenesis can be a viable add-on therapy for the treatment of neuroblastomas. In the present study, we demonstrate that overexpression of secreted protein acidic and rich in cysteine (SPARC) suppresses radiation induced angiogenesis in SK-N-BE(2) and NB1691 neuroblastoma cells. We observed that overexpression of SPARC in SK-N-BE(2) and NB1691 cells reduced radiation induced angiogenesis in an in vivo mouse dorsal skin model and an ex vivo chicken CAM (chorioallantoic-membrane) model and also reduced tumor size in subcutaneous mouse tumor models of NB. We also observed that SPARC overexpression reduces VEGF-A expression, in SK-N-BE(2) and NB1691 NB cells via miR-410, a VEGF-A targeting microRNA. SPARC overexpression alone or in combination with miR-410 and radiation was shown to be effective at reducing angiogenesis. Moreover, addition of miR-410 inhibitors reversed SPARC mediated inhibition of VEGF-A in NB1691 cells but not in SK-N-BE(2) NB cells. In conclusion, the present study demonstrates that the over-expression of SPARC in combination with radiation reduced tumor angiogenesis by downregulating VEGF-A via miR-410.

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Enhanced expression of cohesin loading factor NIPBL confers poor prognosis and chemotherapy resistance in non-small cell lung cancer

Cited by 29 publications

References 42 publications

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

Reduced Expression of Genes Regulating Cohesion Induces Chromosome Instability that May Promote Cancer and Impact Patient Outcomes

SPARC overexpression combined with radiation retards angiogenesis by suppressing VEGF-A via miR-410 in human neuroblastoma cells

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