LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

Dong, Chenhua; Jiang, Tao; Yin, Hang; Hu, Song; Zhang, Yi; Geng, Hao; Shi, Pei-Cong; Xu, Yixin; Gao, Hong; Liu, Lianyu; Zhou, Lei; Zhang, Zhaohui; Song, Jun

doi:10.1038/s41419-021-03602-1

Cited by 24 publications

(15 citation statements)

References 33 publications

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“…In addition, LMNB2 was significantly upregulated in colorectal cancer. LMNB2 upregulation could promote colorectal cancer progression by regulating p21 expression [18]. These previous findings were consistent with our study, emphasizing that LMNB1 and LMNB2 play important roles in tumor progression.…”

Section: Discussionsupporting

confidence: 93%

“…Knockdown of LMNB1 was functionally relevant for melanoma and lung adenocarcinoma (LUAD) progression by influencing cell senescence and DNA damage [16,17]. Upregulation of LMNB2 expression promoted cancer cell proliferation and indicated worse disease-free survival in colorectal cancer and bladder cancer [18,19]. Moreover, lamin family genes play functional roles in the immune system.…”

Section: Introductionmentioning

confidence: 99%

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A Lamin Family-Based Signature Predicts Prognosis and Immunotherapy Response in Hepatocellular Carcinoma

Yang

Xiao

Liu

et al. 2022

Journal of Immunology Research

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Background. Lamin family members play crucial roles in promoting oncogenesis and cancer development. The values of lamin family in predicting prognosis and immunotherapy response remain largely unclarified. Our research is aimed at comprehensively estimating the clinical significance of lamin family in hepatocellular carcinoma and constructing a novel lamin family-based signature to predict prognosis and guide the precise immunotherapy. Methods. The expression features and prognostic value of LMNA, LMNB1, and LMNB2 were explored in the TCGA and GEO databases. The biological functions of LMNB1 and LMNB2 were validated by in vitro assays. A lamin family-based signature was built using the TCGA training set. The TCGA test set, entire TCGA set, and GSE14520 set were used to validate its predictive power. Univariate and multivariate analyses were performed to evaluate the independence of the lamin family-based signature from other clinicopathological characteristics. A nomogram was constructed using the lamin family-based signature and TNM stage. The associations of this signature with molecular pathways, clinical characteristics, immune cell infiltration, and immunotherapy response were analyzed. Results. Lamin family members were upregulated in HCC. Upregulation of LMNB1 and LMNB2 promoted HCC proliferation, migration, and invasion. The predictive signature was initially established based on LMNB1 and LMNB2 which could effectively identify differences in overall survival, immune cell infiltration, and clinicopathological characteristics of high- and low-risk patients. The nomogram showed high prognostic predictive accuracy. Importantly, the lamin family-based signature was correlated with immune suppression and expression of immune checkpoint molecules. Conclusions. The lamin family-based signature is a robust biomarker to predict overall survival and immunotherapy response in HCC. High-risk score patients have a poorer overall survival and might be more sensitive to immunotherapy. This signature may contribute to improving individualized prognosis prediction and precision immunotherapy for HCC patients.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

A Lamin Family-Based Signature Predicts Prognosis and Immunotherapy Response in Hepatocellular Carcinoma

Yang

Xiao

Liu

et al. 2022

Journal of Immunology Research

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“…LMNB2 is a chromatin remodeling protein that also plays a role in eukaryotic cell proliferation by organizing the nuclear membrane during mitosis. Chen-Hua Dong et al recently found that high expression of LMNB2 in CRC tumors correlates with worse disease-free cumulative and overall survival, and that LMNB2 promotes the progression of colorectal cancer by silencing p21 expression [ 38 ]. In line with this, we found that young CRC patients, who tend to express high levels of BRCA1 in their tumors, also tend to express low levels of p21 and this may be due to simultaneous high expression of LMNB2 (Supplementary Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, here we observe that young/BRCA1 mRNA-high CRC patients also more frequently expressed low levels of p21 compared to older/BRCA1 mRNA-low CRC patients (Supplementary Table 2). This may be due to the correlation of BRCA1 mRNA expression with LMNB2 expression specifically in CRC ( Figure 5D ), as LMNB2 has been shown to silence p21 expression [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Opposing effects of BRCA1 mRNA expression on patient survival in breast and colorectal cancer and variations among African American, Asian, and younger patients

2021

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Breast cancer (BC) and colorectal cancer (CRC) are common and show poor survival in advanced stages. Using The Cancer Genome Atlas (TCGA) computational tool cBioPortal, we evaluated overall patient survival in BRCA1 mRNA-low versus -high cohorts (<−1.29 versus >1.05 SD from mean BRCA1 expression, respectively). Analysis included 1082 BC patients with mRNA data (PanCancer Atlas), 382 CRCs (Firehose Legacy) and 592 CRCs (PanCancer Atlas). As previously reported, BRCA1 mRNA-low tumor expression positively correlated with BC patient survival but was negatively associated in CRC. We observed a correlation between BRCA1 mRNA-high and age <45 years at CRC diagnosis using a Fisher’s exact test [Firehose Legacy database ( p -value = 0.0091); CRC PanCancer Atlas ( p -value = 0.0778)]. We correlated BRCA1 mRNA-low expression and basal BC ( p -value = 0.0016) and BRCA1 mRNA-low tumors and frequency of African American patients ( p -value = 0.0448) with BC. Other trends included higher frequency of advanced lymph node stage and mucinous adenocarcinoma among BRCA1 mRNA-low CRC and higher frequency of males in BRCA1 mRNA-high BC and CRC. African Americans more frequently had BRCA1 mRNA-low BC and BRCA1 mRNA-high CRC and the opposite was observed among Asians. Using a gene co-expression tool (cBioPortal), we observed TOP2A and ATAD5 levels correlate (Spearman’s correlation>0.6) with BRCA1 in BC and CRC, whereas LMNB2 correlates with BRCA1 in CRC, suggesting tissue-specific BRCA1 interactions. Our results indicate potential for BRCA1 mRNA expression levels as a prognostic biomarker in BC and CRC, suggest tissue-specificity in BRCA1 molecular interactions, and point to BRCA1 mRNA-high levels as a characteristic of CRC tumors in younger versus older individuals.

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“…Furthermore, our study is the first to find significant upregulation of LMNB2 in EC. LMNB2 is a lamin protein known to regulate nuclear stability and gene expression [ 39 ], with noted upregulation in breast, colorectal and oesophageal cancers [ 40 , 41 , 42 ]. Our in silico study notes LMNB2 to be highly expressed in all EC subtypes, with unique upregulation in HGEC and G3 endometrioid cancer.…”

Section: Discussionmentioning

confidence: 99%

Role of Nucleolin in Endometrial Precancerous Hyperplasia and Carcinogenesis: Ex Vivo and In Silico Study

Barzilova

Drury

Rogers

et al. 2022

IJMS

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Endometrial cancer (EC) is the most common gynaecological malignancy. Nucleolin (NCL) is involved in rDNA transcription, cell proliferation, and apoptosis, with high expression associated with worse overall survival (OS) in other adenocarcinomas. Our aims were to assess NCL gene and protein expression and explore the differential expression of NCL-associated genes (NAGs) in endometrial carcinogenesis. Endometrial samples were obtained from 157 women to include healthy, hyperplastic (EH), EC, and metastatic groups. RT-qPCR and immunohistochemistry were employed to assess NCL gene and protein levels. In silico analysis of NAGs in TCGA and GEO datasets was performed, with the prognostic value determined via Human Protein Atlas. NCL mRNA level of EC was lower than in healthy post-menopausal endometrium (p < 0.01). EH samples had lower NCL immuno-expression scores than healthy pre-menopausal (p < 0.001), benign post-menopausal (p < 0.01), and EC (p < 0.0001) samples. Metastatic lesions demonstrated higher NCL quick scores than primary tissue (p = 0.04). Higher NCL Immuno quick scores carried a worse OS in high-grade EC (p = 0.01). Interrogating Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) and Uterine Carcinosarcoma (TCGA-UCS) cohorts revealed NCL to be the most highly upregulated gene in carcinosarcoma, with S100A11, LMNB2, RERG, E2F1 and CCNA2 representing key dysregulated NAGs in EC. Since NCL is implicated in transforming hyperplastic glands into cancer, with further involvement in metastasis, it is suggested to be a promising target for better-informed diagnosis, risk stratification, and management of EC.

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LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

Cited by 24 publications

References 33 publications

A Lamin Family-Based Signature Predicts Prognosis and Immunotherapy Response in Hepatocellular Carcinoma

A Lamin Family-Based Signature Predicts Prognosis and Immunotherapy Response in Hepatocellular Carcinoma

Opposing effects of BRCA1 mRNA expression on patient survival in breast and colorectal cancer and variations among African American, Asian, and younger patients

Role of Nucleolin in Endometrial Precancerous Hyperplasia and Carcinogenesis: Ex Vivo and In Silico Study

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