The High Expression of RRM2 Can Predict the Malignant Transformation of Endometriosis

Yang, Bin; Li, Na; Zhang, Wenwen; Hu, Yuanjing

doi:10.1007/s12325-021-01888-3

Cited by 13 publications

(13 citation statements)

References 31 publications

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“…Previous studies concurred that increased RRM2 activity was tightly associated with tumor progression and malignancy [ 18 , 28 ]. For example, RRM2 elevated expression in mice markedly cooperated with activated oncogenes and drove malignancy [ 29 ].…”

Section: Discussionsupporting

confidence: 56%

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Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer

Zhou

Song

Yang

et al. 2022

Cancers

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As a crucial subunit of ribonucleotide reductase, RRM2 plays a significant part in DNA synthesis. This study aimed to elucidate the comprehensive landscape of RRM2 in human cancers. With different bioinformatics platforms, we investigated the expression pattern, prognostic significance, mutational landscapes, gene interaction network, signaling pathways and immune infiltration of RRM2 in tumors. We found that RRM2 expression was predominantly up-expressed in tumor tissues in most tumors. Concurrently, RRM2 expression was significantly associated with worse prognosis and tumor stage across TCGA cancers. Moreover, RRM2 high levels were critically associated with the infiltration of natural killer T cells and immune scores. RRM2 was positively related to immune checkpoints, tumor mutation burden, microsatellite instability, neoantigen, and cytotoxic T lymphocyte in several cancers, predicting effective response to immunotherapy. Meanwhile, a strong co-expression of RRM2 with immune-related genes was observed. Additionally, multiple Cox regression analysis showed that RRM2 was an independent prognostic factor in bladder cancer (BLCA). Eventually, we verified that RRM2 was overexpressed in BLCA clinical samples and cell lines. Blocking RRM2 could suppress BLCA cells’ growth and proliferation while enhancing sensitivity to cisplatin. This study provided a new perspective for understanding RRM2 in cancers and new strategies for tumor immunotherapy.

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Section: Discussionsupporting

confidence: 56%

“…For instance, RRM2 could significantly and specifically promote colon cancer (CRC) cell growth [ 16 ]. Consequently, RRM2 overexpression plays a critical part in the proliferation, metastasis and drug dependence of human cancers [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer

Zhou

Song

Yang

et al. 2022

Cancers

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“…A study on bovine preimplantation embryonic development pointed out that mRNA POSTN was identified in in vitro culture media as an indicator of embryo quality [ 24 ]. RRM2 has been widely explored in cancer diseases, and its expression was found to be increased in women with endometriosis-associated ovarian cancer while reduced in women with endometriosis [ 25 ]. Based on the DE-circRNA and DE-miRNA interactions in RIF, there were several circRNAs showing same expression patterns as KDR, POSTN, and RRM2 in RIF were identified, including hsa_circ_001572, hsa_circ_001884, hsa_circ_001375, hsa_circ_001449, hsa_circ_000029, hsa_circ_001168, hsa_circ_000210, hsa_circ_001484, hsa_circ_001698, and hsa_circ_000089.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of circRNA-Mediated ceRNA Regulatory Networks in relation to Recurrent Implantation Failure

Wang

Zhu

2022

Evidence-Based Complementary and Alternative Medicine

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Recurrent implantation failure (RIF) is attributed to endometrial receptivity dysfunction with many unanswered questions. Up to now, there is no explanation for RIF, and therapeutic strategies are usually limited to supportive care. In this study, we differentially analyzed the raw data deposited in three eligible microarray datasets, GSE111974, GSE121219, and GSE147442 to screen DE-mRNAs, DE-miRNAs, and DE-circRNAs, respectively. The value of log2-fold change |log2FC| ≥ 1 and the adjusted p value < 0.05 were considered differentially expressed between RIF and fertile control. We found 350 DE-mRNAs, 43 DE-miRNAs, and 1968 DE-circRNAs between RIF and fertile control. The PPI network identified 6 hub genes with degree ≥10, KDR, AGT, POSTN, TOP2A, RRM2, and PTGS2, in RIF. KDR, AGT, POSTN, TOP2A, and RRM2 were downregulated in endometrial tissue samples of RIF compared with those of fertile control, while PTGS2 was upregulated in endometrial tissue samples of RIF compared with those of fertile control. According to the ceRNA hypothesis, 15 groups of ceRNA network based on 10 circRNAs, hsa_circ_001572, hsa_circ_001884, hsa_circ_001375, hsa_circ_001449, hsa_circ_000029, hsa_circ_001168, hsa_circ_000210, hsa_circ_001484, hsa_circ_001698, and hsa_circ_000089 were constructed in RIF. In conclusion, the present study examined the possible role of circRNAs and their related ceRNA network involved in the pathogenesis of RIF.

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“…The RRM2 is a proteincoding gene that encodes one of two non-identical subunits for ribonucleotide reductase and is highly expressed in the bone marrow (28.1) and lymph node (20.5), along with other tissues [30]. The high expression of this gene can lead to the abnormal proliferation of histiocytes and can also be used as a marker for malignant changes in ovarian endometriosis [31]. The rs72619992 variant in LOC105377644 is an uncharacterized RNA gene that belongs to the ncRNA class and does not code for any protein.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits

Udosen¹,

Soremekun²,

Kamiza³

et al. 2023

Preprint

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Background: High blood pressure (BP) has been implicated as a major risk factor for cardiovascular diseases in several global populations, including in individuals of African ancestry. Despite the elevated burden of high BP-induced cardiovascular diseases in Africa and other global populations with African ancestry, limited genetic studies have been carried out to explore the genetic machinery driving this phenomenon. Methods: We performed univariate and multivariate analyses using Genome-wide association studies (GWAS) and summary statistics data of 77,850 individuals of African ancestry for systolic (SBP) and diastolic blood pressure (DBP) traits. The six independent cohorts used included individuals derived from the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). Subsequently, we annotated, prioritized, visualized, and interpreted our meta-analyses results using FUMA, to gain further insight into the molecular mechanism(s) that contribute to the genetics of BP traits. Finally, loci attaining genome-wide significance, GWS (p<5x10-8) were also followed up with Bayesian fine-mapping to identify potential causal variants. Results: Our meta-analyses altogether identified 350 GWAS SNPs for SBP (166 SNPs) and DBP (184 SNPs, including two novel loci) whilst our multivariate GWAS method identified 166 SNPs (including three novel loci). Interestingly, in FUMA there was significant tissue enrichment of up-regulated differentially expressed genes (DEGs) in the sigmoid and transverse colon for SBP, as well as 10 significant gene sets from MAGMA gene set analyses, However, for DBP, no significant DEGs nor gene sets in MAGMA were found; instead, in DBP for gene property analysis for tissue specificity nine candidates were found to be significant and all nine were in different brain regions. Finally, Bayesian fine-mapping revealed that only 11 variants from the lead SNPs had >50% posterior probability (PP) of being causal and they included novel variant rs562545 (MOBP, PP = 77%) and 10 other previously published variants. Conclusion: Our results demonstrate the importance of performing GWAS in large sample sizes of global populations of African ancestry, including continental Africans; which yield novel insights, from novel loci to novel pathways/tissue expression candidates. Large-scale genomic datasets are required to enhance further discovery and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits. Our study highlights the need for diversity in genetic research and the importance of expanding large GWASs to include ancestrally diverse populations.

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The High Expression of RRM2 Can Predict the Malignant Transformation of Endometriosis

Cited by 13 publications

References 31 publications

Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer

Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer

Comprehensive Analysis of circRNA-Mediated ceRNA Regulatory Networks in relation to Recurrent Implantation Failure

Meta-analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits

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