RRM2 overexpression

RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.

We developed paclitaxel-, doxorubicin-, and cisplatin-resistant MDA-MB-231 cells to study MYC's role in upregulating DNA repair genes during drug resistance development...The combined use of asiRNA-VP (Vinylphosphonate) with dacomitinib or talazoparib was synthetic lethal in TNBC cell lines...We confirmed that MYC knockdown upregulated cFLIP, BCL2, STAT1, pSTAT1, STAT2, and cleaved saspase-3 in both TNBC and non-small cell lung cancer (NSCLC) cell lines. Finally, we recommend a combination treatment approach that synergizes with MYC inhibition rather than monotherapy or indirect targeting via upstream regulators such as the BRD4 and RRM2 genes or selective modulation at the protein level to suppress anti-apoptotic genes (cFLIP and BCL2) at the same time.

FOXM1-induced IGF2BP3 upregulation promotes HCC cell malignant behaviors and macrophages M2 polarization by repressing ferroptosis via m6A-dependent regulation of RRM2 mRNA. Targeting FOXM1/IGF2BP3/RRM2 to enhance ferroptosis might be exploited as a potent therapeutic strategy for HCC.

Furthermore, bifonazole exhibited antitumor effects on ESCC patient-derived xenograft (PDX) models by decreasing RRM2 expression and the dNTP pool. In summary, this study reveals the interaction network among HuR, RRM2, and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.

The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target.

Our study uncovered a novel molecular mechanism of lncRNA SNHG4 in driving prostate cancer progression and enzalutamide resistance, revealing the critical roles and therapeutic potential of RREB1, SNHG4, RRM2 and let-7 miRNAs in anticancer therapy.

RRM2 expression is significantly elevated in NF1-associated MPNST and that high RRM2 expression correlates with poorer outcomes. RRM2 acts as an integral part in the promotion of NF1-associated MPNST cell proliferation via the AKT-mTOR signaling pathway. Inhibition of RRM2 may be a promising therapeutic strategy for NF1-associated MPNST.

Over-expression of RRM2 predict adverse prognosis and is correlated with immune infiltrates in HCC. RRM2 may be a significant molecular biomarker for HCC diagnosis and prognosis.

This study provides multi-layered and multifaceted evidence for the importance of HMMR and establishes a HMMR-related ceRNA (HEELPAR-hsa-let-7i-5p-RRM2) overexpressed network related to the prognosis of gliomas.

The high expression of PRMT1 in NPC inhibits apoptosis of NPC cells by promoting the expression of RRM2.

Circ_0006646 was highly expressed in the exosomes of CC patients. Circ_0006646 expedited CC cell growth and metastasis by regulating miR-758-3p/RRM2 axis, and exosomal circ_0006646 might be a potential diagnostic indicator of CC.

Finally, we identified miR-219a-2-3p as a potential target of RRM2-C2orf48 in lung cancer. In summary, chimeric RNA RRM2-C2orf48 accelerated the process of NNK-induced lung cancer, and miR-219a-2-3p may be involved in this process.

In this study, circ_0008285 could promote the malignant biological behaviors of HCC cells through miR-384/RRM2 axis and has the potential to become a therapeutic target for HCC, providing a new idea for targeted therapy of HCC.

Moreover, expression of RRM2 was negatively correlated with ARID1A in pancreatic cancer tissues. Thus, ARID1A-mediated RRM2 epigenetic suppression is crucial for enhancement of pancreatic cancer chemosensitivity to gemcitabine, and ARID1A could be used as a biomarker to guide the gemcitabine chemotherapy of pancreatic cancer.

Our findings show that melanoma BM harbor distinct immunosuppressive mechanisms compared to primary tumors: this data elicits the importance of investigating the heterogeneity of BM microenvironment. Genes and pathways selectively overexpressed or downregulated in melanoma BM should be validated to be possibly considered as novel therapeutic targets.

In addition, RRM2 expression was significantly positively related to immune cell infiltration, immune cell biomarker or immune checkpoint expression in HCC. Altogether, the upregulation of RRM2 mediated by ncRNAs correlates with poor prognosis and tumor immune infiltration of HCC.

In vitro, RRM2 inhibition enhances intrinsic replication stress checkpoint addiction. Last, combinatorial RRM2-CHK1 inhibition acts synergistic in high-risk neuroblastoma cell lines and patient-derived xenograft models, illustrating the therapeutic potential.

MiR-200c-3p or miR-485-5p enhanced the DDP sensitivity and suppressed the malignant behaviors of NSCLC cells partly through targeting RRM2.

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.

Clinical data analysis revealed that RRM2 expression in glioma patients was inversely correlated with the overall survival. Collectively, pectolinarigenin promoted the degradation of CDK1 protein dependent on autolysosomal pathway through increasing autophagic flux by inhibiting RRM2, thereby inhibiting the proliferation of glioblastoma cells by inducing G2/M phase cell cycle arrest, and RRM2 may be a potential therapeutic target and a prognosis and predictive biomarker in GBM patients.

However, miR-582-3p depleted RRM2 expression, thereby attenuating the oncogenic effects of RRM2. In conclusion, our results demonstrated that miR-582-3p binds to RRM2 to regulate the Wnt/β-catenin signaling pathway, thereby blocking the progression of HCC.

LncRNA HOTAIR upregulated RRM2 by competitively binding to miR-20b-5p and activated PI3K/AKT pathway, thereby facilitating proliferation and repressing apoptosis of RB cells.

Collectively, our data indicate that RRM2 promotes the progression of RB by activating JAK2/STAT3 signaling pathway. Targeting RRM2/JAK2/STAT3 axis lays a theoretical foundation for the formulation of novel RB therapy.

Furthermore, we show that exhausted CD4 T cells induced the expression of the RRM2 gene in the primary ccRCC cell line. Collectively, our results provide the link between PBRM1 loss, RRM2 expression and T cell infiltration, which may lead to the establishment of new treatment of this disease.

Furthermore, overexpressing RRM2 induces DOX resistance of HT1080 cells by rescuing DOX-induced DNA damage by promoting DNA repair, whereas CYP1A2 confers resistance by decreasing intracellular DOX accumulation, which piR-39980 restores. This study reveals that piR-39980 could reduce fibrosarcoma resistance to DOX by modulating RRM2 and CYP1A2, implying that piRNA can be used in combination with DOX.

Further, overexpression of RRM2 in HT1080 cells induces proliferation, migration, invasion, and colony formation, whereas its silencing arrest the cell cycle at G0/G1 phase and induces apoptosis. Taken together, we established RRM2 to be positively associated with oncogenesis and prognosis of STS and therefore could be a promising prognostic marker and therapeutic target.

The miR-30a-5p/RRM2 axis facilitated the malignant transformation of PDAC cells.

GEPIA Box Plot showed that BUB1, CCNB2, PTTG1, and RRM2 were over expressed in the ccRCC tissues in contrast to the normal tissues (P<0.05). Conclusion ccRCC patients with the four up-regulated differentially expressed genes including BUB1,CCNB2,PTTG1, and RRM2might manifest a poor prognosis.

Altogether, we propose a signature network of E3 ligases that collaboratively modulates CCNF anti-cancer activity. There is potential to target BRCA through modulation of the partnership axes of (i) CCNF-FBXL8, (ii) CCNF-FZR1, and (iii) CCNF-RRM2, particularly, via CCNF overexpression and activation and FBXL8/FZR1 suppression.

Our results show that the oncolytic effects of MYXV correlate directly with RR expression levels and are enhanced in STS cell lines with naturally occurring or artificially induced high expression levels of RR. Myxoma virus holds promise in the treatment of advanced soft tissue cancer, especially in tumors overexpressing RR.

This synthetic lethal effect reflected conversion of single-stranded lesions in IGF-inhibited cells into toxic DSBs upon ATM inhibition. Overall, these data implicate IGF-1R in alleviating replication stress, and the reciprocal IGF:ATM co-dependence we identify provides an approach to exploit this effect in ATM-deficient cancers.

Ribonucleotide reductase M2 may be a novel target in the diagnosis, prognosis, and therapy of OSCC.

RRM2 over-expression increased the activation of Bcl-2 and E-cadherin signaling pathways, and reduced the activation of p53 signaling pathway. In summary, high RRM2 expression is an independent predictive factor of poor prognosis in patients with lung adenocarcinoma.

It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.