RRM2 is a potential prognostic biomarker with functional significance in glioma

Sun, Hongmei; Yang, Bo; Zhang, Hao; Song, Jingwei; Zhang, Yenan; Xing, Jing; Yang, Zhihui; Wei, Changyong; Xu, Tianhua; Yu, Zhiyang; Xu, Zhipeng; Hou, Min; Ji, Minjun; Zhang, Yansong

doi:10.7150/ijbs.30114

Cited by 51 publications

(44 citation statements)

References 44 publications

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“…Furthermore, we explored the functional target of miR-338-3p in glioma. RRM2 has been revealed as an oncogene that promotes glioma cell proliferation and migration [24]. Here we validated RRM2 as a functional The RRM2 abundances at mRNA (A) and protein (B) levels were measured in A172 and U251 cells transfected with pcDNA3.1, pcDNA3.1/ KCNQ1OT1, pcDNA3.1/KCNQ1OT1 and miR-NC or miR-338-3p by qRT-PCR and western blot analysis.…”

Section: Overexpression Of Kcnq1ot1 Up-regulates Rrm2 Expression By Dmentioning

confidence: 77%

“…including bladder cancer, melanoma and oral squamous cell carcinoma [17][18][19]. Moreover, previous research has suggested that dysregulation of miR-338-3p is involved in glioma malignancy [20][21][22], and that Ribonucleotide reductase M2 (RRM2) may contribute to development of glioma [23,24]. More importantly, predictions using starBase 2.0 indicate potential complementary sequences between miR-338-3p and KCNQ1OT1 or RRM2, however sequence interactions between these targets have not been validated previously.…”

Section: Quantitative Real-time Polymerase Chain Reaction (Qrt-pcr) Fmentioning

confidence: 99%

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Knockdown of lncRNA KCNQ1OT1 inhibits glioma progression by regulating miR-338-3p/RRM2

et al. 2020

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AbstractThe dysregulated lncRNA play essential roles in glioma development. This study aimed to investigate the role and mechanism of lncRNA potassium voltage-gated channel subfamily Q member 1 opposite strand/ antisense transcript 1 (KCNQ1OT1) in glioma progression. Tumor tissues and adjacent normal samples were collected from 30 glioma patients. The expression levels of lncRNA KCNQ1OT1, microRNA (miR)-338-3p and ribonucleotide reductase M2 (RRM2) were detected by quantitative real-time polymerase chain reaction or western blot analyses. Levels of cell viability, apoptosis, cell migration and invasion in glioma cell lines were determined using cell counting kit-8, flow cytometry with annexin V-FITC and trans-well assays, respectively. The role of KCNQ1OT1 in glioma development in vivo was investigated using a xenograft model. The target association between miR-338-3p and KCNQ1OT1 or RRM2 was validated by luciferase reporter assay. The results found that expression of KCNQ1OT1 was enhanced in glioma tissues and cells, and KCNQ1OT1 knockdown inhibited cell viability, migration and invasion, and xenograft tumor growth, but promoted apoptosis. miR-338-3p was targeted via KCNQ1OT1 and could reverse the effect of KCNQ1OT1 on glioma progression. RRM2 was targeted via miR-338-3p and attenuated the suppressive effect of miR-338-3p on glioma cell viability, migration and invasion. Besides, KCNQ1OT1 overexpression increased RRM2 expression, and this event was weakened via miR-338-3p up-regulation. In conclusion, the present finding suggest that silencing of KCNQ1OT1 can suppress the development and progression of glioma by up-regulating miR-338-3p and down-regulating RRM2.

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Section: Overexpression Of Kcnq1ot1 Up-regulates Rrm2 Expression By Dmentioning

confidence: 77%

Section: Quantitative Real-time Polymerase Chain Reaction (Qrt-pcr) Fmentioning

confidence: 99%

Knockdown of lncRNA KCNQ1OT1 inhibits glioma progression by regulating miR-338-3p/RRM2

et al. 2020

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“…The dysregulated cell cycle has been identified in many types of cancer 29 . Ribonucleotide reductase is an enzyme involved in the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Independent prognostic implications of RRM2 in lung adenocarcinoma

Luo

Cao

et al. 2020

J. Cancer

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Background: Ribonucleoside-diphosphate reductase subunit M2 ( RRM2 ) is the catalytic subunit of ribonucleotide reductase and modulates the enzymatic activity, which is essential for DNA replication and repair. However, the role of RRM2 in lung adenocarcinoma (LUAD) remains unclear. Methods: In this study, we explored the expression pattern and prognostic value of RRM2 in LUAD across TCGA, GEO, Oncomine, UALCAN, PrognoScan, and Kaplan-Meier Plotter, and confirmed its independent prognostic value via Cox analyses. LinkedOmics and GEPIA2 were applied to investigate co-expression and functional networks associated with RRM2 . Besides, we used TIMER to assess the correlation between RRM2 and the main six types of tumor-infiltrating immune cells. Lastly, the correlations between immune signatures of immunomodulators, chemokines, and 28 tumor-infiltrating lymphocytes (TILs) and RRM2 were examined by tumor purity-corrected partial Spearman's rank correlation coefficient through TIMER portal. Results: RRM2 was found upregulated in tumor tissues in TCGA-LUAD, and validated in multiple independent cohorts. Moreover, whether in TCGA or other cohorts, high RRM2 expression was found to be associated with poor survival. Cox analyses showed that high RRM2 expression was an independent risk factor for overall survival, disease-specific survival, and progression-free survival of LUAD. Functional network analysis suggested that RRM2 regulates RNA transport, oocyte meiosis, spliceosome, ribosome biogenesis in eukaryotes, and cellular senescence signaling through pathways involving multiple cancer-related kinases and E2F family. Also, RRM2 expression correlated with infiltrating levels of B cells, CD4+ T cells, and neutrophils. Subsequent analysis found that B cells and dendritic cells could predict the outcome of LUAD. B cells were identified as an independent risk factor among six types of immune cells through Cox analyses. At last, the correlation analysis showed RRM2 correlated with 67.68% (624/922) of the immune signatures we performed. Conclusion: Our research showed that RRM2 could independently predict the prognosis of LUAD and was associated with immune infiltration. In particular, the tight relationship between RRM2 and B cell marker genes are the potential epicenter of the immune response and one of the critical factors affecting the prognosis. Our findings laid the foundation for further research on the immunomodulatory role of RRM2 in LUAD.

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“…Another example was RRM2 and BRIP1, which was significantly correlated with each other in expression ( Figure 6C, R = 0.93 and p-value < 0.001). RRM2 had been found to promote the progression of human GBM and was a potential prognostic biomarker in glioma (Li et al, 2018a;Sun et al, 2019). BRIP1 was found to be an independent signature, which was correlated with worse prognosis in glioma (de Sousa et al, 2017).…”

Section: Rna-binding Protein Regulatory Network During Glioma Progresmentioning

confidence: 93%

Systematically Dissecting the Function of RNA-Binding Proteins During Glioma Progression

Wang

Hou

2020

Front. Genet.

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RNA-binding proteins (RBPs) play important roles in regulating gene expression and dysregulation of RBPs have been observed in various types of cancer. However, the role of RBPs during glioma progression, and particular in Chinese patients, is only starting to be unveiled. Here, we systematically analyzed the somatic mutation, gene expression patterns of 2949 RBPs during glioma progression. Our comprehensive study reveals several of highly mutated genes (such as ATRX, TTN and SETD2) and differentially expressed genes (such as KIF4A, TTK and CEP55). Integration of the expression of RBPs and genes, we constructed a regulatory network in glioma and revealed the functional links between RBPs and cancer-related genes. Moreover, we identified the prognosis spectrum of RBPs during glioma progression. The expression of a number of RBPs, such as SNRPN and IGF2BP3, are significantly associated with overall survival of patients in all grades. Taken together, our analyses provided a valuable RBP resource during glioma progression, and revealed several candidates that potentially contribute to development of therapeutic targets for glioma.

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RRM2 is a potential prognostic biomarker with functional significance in glioma

Cited by 51 publications

References 44 publications

Knockdown of lncRNA KCNQ1OT1 inhibits glioma progression by regulating miR-338-3p/RRM2

Knockdown of lncRNA KCNQ1OT1 inhibits glioma progression by regulating miR-338-3p/RRM2

Independent prognostic implications of RRM2 in lung adenocarcinoma

Systematically Dissecting the Function of RNA-Binding Proteins During Glioma Progression

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