DNA primase polypeptide 1 (PRIM1) involves in estrogen‐induced breast cancer formation through activation of the G2/M cell cycle checkpoint

Lee, Wei Hwa; Chen, Li‐Ching; Chia‐Jung, Lee; Huang, Chi‐Cheng; Ho, Yuan‐Soon; Yang, Po‐Sheng; Ho, Chi‐Tang; Chang, Hang‐Lung; Lin, I‐Hsuan; Chang, Hui‐Wen; Liu, Yun‐Ru; Wu, Chih‐Hsiung; Tu, Shih Hsin

doi:10.1002/ijc.31788

Cited by 28 publications

(30 citation statements)

References 46 publications

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“…On the one hand, estrogen acts as a cancer promoter by increasing mitosis of mammary duct epithelial cells. The mechanism may be that as the initiator of cancerization, estrogen metabolites can bind to DNA, then directly cause DNA damage and genetic mutations (36).…”

Section: Discussionmentioning

confidence: 99%

miR-452 Reverses Abnormal Glycosylation Modification of ERα and Estrogen Resistance in TNBC (Triple-Negative Breast Cancer) Through Targeting UGT1A1

Zhou

Mao

et al. 2020

Front. Oncol.

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Background: The breast epithelial cells in patients with triple-negative breast cancer (TNBC) actually have specific estrogen receptor (ER) expression, and the abnormal glycosylation of UGT1A1 in TNBC cells resulted in abnormal expression and function of ERα through regulating the modification of ERα. Therefore, our study targets the role of UGT1A1 expression, then glycosylation modification of ERα (estrogen receptor α) and estrogen resistance in development of TNBC. Methods: The differential expression of mRNA and miRNA in TNBC tissues was tested. Luciferase activity was analyzed in TNBC cells treated with miR-452. Moreover, the human mammary gland and TNBC cell lines were dealt with estrogen and miR-452 or its inhibitors, then proliferation ability was further determined. Moreover, the role of interaction between UGT1A1 and ERα in the glycosylation modification of ERα and UGT activity, and metabolism of estrogen were assessed. The effects of miR-452 on TNBC by improving abnormal glycosylation modification of ERα by targeting UGT1A1 and estrogen resistance were studied in vitro and in vivo. Results: The expression level of UGT1A1 in TNBC tumor tissues was higher than its matched para-tumorous tissues, but the miR-452 expression was opposite. The glycosylation modification site of ERα expressed in TNBC cells was different from that of normal mammary epithelial cells. The estrogen 17β-estradiol (E2) significantly promoted mitotic entry of TNBC cells. The interaction between UGT1A1 and ERα affected the expression level of each other, as well as the UGT enzyme activity and proliferation of TNBC cells. UGT1A1 induced production of intracellular estrogens and TNBC proliferation, but it could be reversed by overexpression of ERα. Upregulation of ERα caused the downregulation of UGT1A1 and marked decrease of intracellular estrogen products, and then suppressed TNBC proliferation. Moreover, UGT1A1 was the target gene of miR-452; miR-452 antagomir restrained TNBC xenograft. Li et al. miR-452 Reverses TNBC Estrogen Resistance Conclusion: Our results demonstrated that estrogen was a positive factor in the proliferation of TNBC cells at onset of mitosis through accentuating the expression and enzyme activity of UGT1A1. However, miR-452 targeted to UGT1A1, then regulated glycosylation modification of ERα, estrogen metabolism, and TNBC development associated with estrogen resistance.

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Section: Discussionmentioning

confidence: 99%

miR-452 Reverses Abnormal Glycosylation Modification of ERα and Estrogen Resistance in TNBC (Triple-Negative Breast Cancer) Through Targeting UGT1A1

Zhou

Mao

et al. 2020

Front. Oncol.

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“…PRIM1 aberrations affect the cell cycle transition from G1 to S phase. And previous studies have proved that PRIM1 is over-expressed in various malignant tumor cells such as osteosarcoma [16], bladder carcinoma [17], breast cancer [12], and glioma [18]. Wurmbach et al also reported that PRIM1 was up-regulated in HCC tissues [19]; however, its specific role in development of HCC and other cancers is still undefined.…”

Section: Ivyspringmentioning

confidence: 99%

PRIM1 promotes the proliferation of hepatocellular carcinoma cells in vitro and in vivo

Jiang

Zhang

et al. 2020

J. Cancer

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PRIM1 plays an important role during oncogenesis, however it has never been reported in liver cancer, and thus our objective is to explore the role of PRIM1 in liver cancer. We selected RNAseq data of 50 paired liver cancer samples from the Cancer Gene Atlas (TCGA), and then bioinformatics methods and Mann-Whitney U test were used to analyze the correlation between PRIM1 and the clinical pathological stage of liver cancer. Quantitative polymerase chain reaction (QPCR) was used to detect mRNA expression of PRIM1 in BEL-7404, BCL-7402, HepG2 and SMMC-7721 cell lines. LV-PRIM1-RNAi was transfected into BEL-7404 and SMMC-7721 cells by lentivirus, and then Celigo imaging cytometer, Caspase3/7 Assay, flow cytometry and MTT assay were used to detect the proliferation and apoptosis of BEL-7404 and SMMC-7721 cells with ≥50% gene reduction rate after lentivirus transfection detected by QPCR. BEL-7404 and SMMC-7721 carrying PRIM1 gene were used for oncogenesis in vitro to observe the weight and fluorescence intensity of the tumor. Bioinformatics method was used to obtain the information about PRIM1 gene, and the correlation between PRIM1 and clinical pathological stage of liver cancer was analyzed by Mann-Whitney U test. QPCR results showed that PRIM1 was expressed in BEL-7404, BCL-7402, HepG2 and SMMC-7721 cell lines, which was highest in BCL-7404 cell line. Celigo imaging cytometer, Caspase3/7 Assay, flow cytometry and MTT assay showed that the proliferative ability of BEL-7404 and SMMC-7721 were decreased after LV-PRIM1-RNAi transfection. Furthermore, the weight and the fluorescence intensity of the tumors in vitro formed by LV-PRIM1-RNAi cells on SCID mice were decreased. So, interference of PRIM1 expression can inhibit the proliferation of BEL-7404 and SMMC-7721 cells, as well as induce the apoptosis of liver cancer cells.

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“…The DNA primase polypeptide 1 (PRIM1) is responsible for synthesizing small RNA primers for Okazaki fragments generated during discontinuous DNA replication, the DNA replication cannot proceed without the catalytic function of PRIM1, thus PRIM1 is an vital role in the initiation (priming) of the DNA replication, and its aberrations may play a key tumorigenic factor by affecting the cell cycle transition from G1 to S phase (Yotov et al, 1999). So far, PRIM1 have been reported be associated with the formation of breast cancer (Lee et al, 2019b).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma

Zhu

et al. 2020

PeerJ

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Background Due to the complicated molecular and cellular heterogeneity in hepatocellular carcinoma (HCC), the morbidity and mortality still remains high level in the world. However, the number of novel metabolic biomarkers and prognostic models could be applied to predict the survival of HCC patients is still small. In this study, we constructed a metabolic gene signature by systematically analyzing the data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC). Methods Differentially expressed genes (DEGs) between tumors and paired non-tumor samples of 50 patients from TCGA dataset were calculated for subsequent analysis. Univariate cox proportional hazard regression and LASSO analysis were performed to construct a gene signature. The Kaplan–Meier analysis, time-dependent receiver operating characteristic (ROC), Univariate and Multivariate Cox regression analysis, stratification analysis were used to assess the prognostic value of the gene signature. Furthermore, the reliability and validity were validated in four types of testing cohorts. Moreover, the diagnostic capability of the gene signature was investigated to further explore the clinical significance. Finally, Go enrichment analysis and Gene Set Enrichment Analysis (GSEA) have been performed to reveal the different biological processes and signaling pathways which were active in high risk or low risk group. Results Ten prognostic genes were identified and a gene signature were constructed to predict overall survival (OS). The gene signature has demonstrated an excellent ability for predicting survival prognosis. Univariate and Multivariate analysis revealed the gene signature was an independent prognostic factor. Furthermore, stratification analysis indicated the model was a clinically and statistically significant for all subgroups. Moreover, the gene signature demonstrated a high diagnostic capability in differentiating normal tissue and HCC. Finally, several significant biological processes and pathways have been identified to provide new insights into the development of HCC. Conclusion The study have identified ten metabolic prognostic genes and developed a prognostic gene signature to provide more powerful prognostic information and improve the survival prediction for HCC.

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DNA primase polypeptide 1 (PRIM1) involves in estrogen‐induced breast cancer formation through activation of the G2/M cell cycle checkpoint

Cited by 28 publications

References 46 publications

miR-452 Reverses Abnormal Glycosylation Modification of ERα and Estrogen Resistance in TNBC (Triple-Negative Breast Cancer) Through Targeting UGT1A1

miR-452 Reverses Abnormal Glycosylation Modification of ERα and Estrogen Resistance in TNBC (Triple-Negative Breast Cancer) Through Targeting UGT1A1

PRIM1 promotes the proliferation of hepatocellular carcinoma cells in vitro and in vivo

Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma

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