Pumilio Proteins Exert Distinct Biological Functions and Multiple Modes of Post-Transcriptional Regulation in Embryonic Stem Cell Pluripotency and Early Embryogenesis

Uyhazi, Katherine E.; Yang, Yiying; Liu, Na; Qi, Hongying; Huang, Xu; Mak, Winifred; Weatherbee, Scott D.; Song, Xiaoling; Lin, Haifan

doi:10.1101/751909

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…S4a). In the top ten results of principal component analysis (PCA) of the 163 transcription factors, stemness-related PUM1 [ 46 , 47 ], CLOCK [ 48 ], SP1, and TCF12 played a major positive regulatory role in PCa cell stemness (Fig. 3 b and Additional file 8 : Fig.…”

Section: Resultsmentioning

confidence: 99%

High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells

Dai

Liu

2021

J Transl Med

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Background Tumor metastasis is the main cause of death of cancer patients, and cancer stem cells (CSCs) is the basis of tumor metastasis. However, systematic analysis of the stemness of prostate cancer cells is still not abundant. In this study, we explore the effective factors related to the stemness of prostate cancer cells by comprehensively mining the multi-omics data from TCGA database. Methods Based on the prostate cancer transcriptome data in TCGA, gene expression modules that strongly relate to the stemness of prostate cancer cells are obtained with WGCNA and stemness scores. Copy number variation of stemness genes of prostate cancer is calculated and the difference of transcription factors between prostate cancer and normal tissues is evaluated by using CNV (copy number variation) data and ATAC-seq data. The protein interaction network of stemness genes in prostate cancer is constructed using the STRING database. Meanwhile, the correlation between stemness genes of prostate cancer and immune cells is analyzed. Results Prostate cancer with higher Gleason grade possesses higher cell stemness. The gene set highly related to prostate cancer stemness has higher CNV in prostate cancer samples than that in normal samples. Although the transcription factors of stemness genes have similar expressions, they have different contributions between normal and prostate cancer tissues; and particular transcription factors enhance the stemness of prostate cancer, such as PUM1, CLOCK, SP1, TCF12, and so on. In addition, the lower tumor immune microenvironment is conducive to the stemness of prostate cancer. CD8 + T cells and M1 macrophages may play more important role in the stemness of prostate cancer than other immune cells in the tumor microenvironment. Finally, EZH2 is found to play a central role in stemness genes and is negatively correlated with resting mast cells and positively correlated with activated memory CD4 + T cells. Conclusions Based on the systematic and combined analysis of multi-omics data, we find that high copy number variation, specific transcription factors, and low immune microenvironment jointly contribute to the stemness of prostate cancer cells. These findings may provide us new clues and directions for the future research on stemness of prostate cancer.

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Section: Resultsmentioning

confidence: 99%

High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells

Dai

Liu

2021

J Transl Med

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“…4a). In the top ten results of principal component analysis (PCA) of 163 common transcription factors, it was found that stemness-related PUM1 [46,47], CLOCK [48], SP1, and TCF12 played a major positive regulation role on PCa cell stemness (Fig. 3b and Supplementary Fig.…”

Section: The Cnv Of Stemness-related Genes Elevated In Prostate Cancermentioning

confidence: 99%

High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells.

Dai

Liu

2021

Preprint

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Background: Tumor metastasis is the main cause of death of cancer patients, and the existence of cancer stem cells is the basis of tumor metastasis. However, the systematic analysis of the stemness of prostate cancer cells is still not abundant. This article explores the effective factors that lead to the stemness of prostate cancer cells with multi-omics data mining.Methods: Gene expression modules that were strongly related to the stemness of prostate cancer cells were obtained with WGCNA and stemness scores, based on the prostate cancer transcriptome data in TCGA. Calculated the copy number variation of stemness genes of prostate cancer and evaluated the difference of transcription factors in prostate cancer and normal tissues, based on CNV (copy number variation) data and ATAC-seq data. The protein interaction network of stemness genes of prostate cancer was constructed with the STRING database. At the same time, the correlation between stemness genes of prostate cancer and immune cells was analyzed.Results: Prostate cancer with high Gleason grade was more stemness. The gene set highly related to prostate cancer stemness had higher CNV in prostate cancer samples than normal samples. The transcription factors of stemness genes had similar expressions but had different contributions in normal and prostate cancer tissues. And particular transcription factors enhanced the stemness of prostate cancer, such as PUM1, CLOCK, SP1, TCF12, and so on. The lower tumor immune microenvironment was conducive to the stemness of prostate cancer, and CD8+ T cells and M1 macrophages might play an important role than other immune cells in the tumor microenvironment. We also found that EZH2 played a central role in stemness genes and was negatively correlated with resting mast cells and positively correlated with activated memory CD4+ T cells.Conclusions: This study found that high copy number variation, specific transcription factors, and low immune microenvironment contributed to the stemness of prostate cancer cells through systematic multi-omics analysis. These findings would provide new clues and directions for future research of prostate cancer stem cells.

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“…4a). In the top results of principal component analysis (PCA) of 253 common transcription factors, it was found that stemness-related PUM1 [44,45], CLOCK [46], SP1 and TCF12 played a major positive regulation role on PCa cell stemness, while IRF3 [47] was a negative correlation with other 9 transcription factors and played negative regulation role on PCa cell stemness (Fig. 3b, Supplementary Fig.…”

Section: Correlation Analysis Between Cancer Cell Stemness and Clinical Grade In Prostate Cancermentioning

confidence: 99%

Copy Number Variation and Transcription Regulation of Genes and Immune Microenvironment of Tumor Affect the Stemness of Prostate Cancer Cell

Dai¹,

Liu²

2020

Preprint

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Background: Prostate cancer stem cells (pCSC) play an important role in tumor metastasis through multiple pathways. From gene, protein to microenvironment, there are many factors affecting the cell stemness of prostate cancer (PCa). However, the effective factors affecting the stemness of prostate cancer cells are still unclear.Methods: Based on the transcription data of prostate cancer in the TCGA database, WGCNA (Weighted Gene Co-expression Network Analysis) and stemness scores were used to find important stemness gene module. According to ATAC-seq and genomic data, analyze their relationship with stemness. The interaction of stemness genes was analyzed with STRING (functional protein association networks) database. Furthermore, based on the immune microenvironment score, the relationship between immune and stemness was analyzed.Results: The most important stemness gene module in prostate cancer was obtained with WGCNA method; then a positive correlation between the gene CNVs (Copy Number Variants) of the most important stemness gene module and PCa stemness was found, as well as a positive correlation between the gene CNVs and Gleason score of PCa was also drug out. Further, the key transcriptional regulators of the most important stemness genes in PCa were obtained. In addition, it's found that immune cells, especially CD8+T cells and M1 macrophages, suppressed the stemness of PCa cells. Finally, by analyzing the protein interactions and the relationship between genes and immune cells, we found that interaction of the proteins of the most important stemness genes module and the relationship between these genes and immune cells of microenvironment of PCa were all important in affecting the stemness of PCa cells.Conclusions: By analyzing multi-omics data of clinical specimen, we got the most important stemness genes and their important transcriptional regulators in PCa; and further mining analysis showed that the stemness of PCa cells is positive regulated by the CNVs and the interaction of the proteins of the most important stemness genes, and negatively regulated by the immune cells of the microenvironment of prostate cancer.

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Pumilio Proteins Exert Distinct Biological Functions and Multiple Modes of Post-Transcriptional Regulation in Embryonic Stem Cell Pluripotency and Early Embryogenesis

Cited by 4 publications

References 43 publications

High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells

High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells

High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells.

Copy Number Variation and Transcription Regulation of Genes and Immune Microenvironment of Tumor Affect the Stemness of Prostate Cancer Cell

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