High Expression of RRM2 Mediated by Non-coding RNAs Correlates with Poor Prognosis and Tumor Immune Infiltration of Hepatocellular Carcinoma

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2022 Aug 1

PMID 35911380

Authors

Guochao Mao

Lan Li

Changyou Shan

Baobao Liang

Li Ma

Shuqun Zhang

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is known to have a poor prognosis. Accumulating evidence indicates that RRM2 plays a critical role in the occurrence and progression of multiple human cancers. However, the knowledge about RRM2 in HCC is still insufficient, and further research is needed. Here, we first analyzed the expression and prognosis of RRM2 using TCGA and GTEx data, and found that RRM2 may play a potential carcinogenic role in HCC. Then, through a series of comprehensive analysis, including expression analysis, correlation analysis or survival analysis, non-coding RNAs (ncRNAs) that regulate RRM2 overexpression were identified. Finally, MIR4435-2HG/CYTOR were observed to be the most promising upstream lncRNAs for the miR-125b-5p/RRM2 axis in HCC. 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.

Citing Articles

Current insights and future directions of LncRNA Morrbid in disease pathogenesis.

Yang H, Gao J, Zheng Z, Yu Y, Zhang C Heliyon. 2024; 10(17):e36681.

PMID: 39263145 PMC: 11388785. DOI: 10.1016/j.heliyon.2024.e36681.

Characteristics of the immune microenvironment associated with RRM2 expression and its application to PD-L1/PD-1 inhibitors in lung adenocarcinoma.

Lee S, Hwang Y, Han J, Haam S, Lee H, Koh Y Am J Cancer Res. 2023; 13(11):5443-5454.

PMID: 38058821 PMC: 10695782.

Biological Roles and Pathogenic Mechanisms of LncRNA MIR4435-2HG in Cancer: A Comprehensive Review.

Chen Z, Guan D, Zhu Q, Wang Z, Han F, Zhou W Curr Issues Mol Biol. 2023; 45(11):8864-8881.

PMID: 37998733 PMC: 10670187. DOI: 10.3390/cimb45110556.

Computed tomography radiomics signature via machine learning predicts and overall survival in hepatocellular carcinoma.

Li Q, Long X, Lin Y, Liang R, Li Y, Ge L J Gastrointest Oncol. 2023; 14(3):1462-1477.

PMID: 37435222 PMC: 10331770. DOI: 10.21037/jgo-23-460.

MiR-202-3p inhibits the proliferation and metastasis of lung adenocarcinoma cells by targeting RRM2.

Cao X, Xue F, Chen H, Shen L, Yuan X, Yu Y Ann Transl Med. 2023; 10(24):1374.

PMID: 36660663 PMC: 9843311. DOI: 10.21037/atm-22-6089.

References

Sang Y, Chen B, Song X, Li Y, Liang Y, Han D . circRNA_0025202 Regulates Tamoxifen Sensitivity and Tumor Progression via Regulating the miR-182-5p/FOXO3a Axis in Breast Cancer. Mol Ther. 2019; 27(9):1638-1652. PMC: 6731174. DOI: 10.1016/j.ymthe.2019.05.011. View

Schreiber R, Old L, Smyth M . Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. DOI: 10.1126/science.1203486. View

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

Kong Q, Liang C, Jin Y, Pan Y, Tong D, Kong Q . The lncRNA MIR4435-2HG is upregulated in hepatocellular carcinoma and promotes cancer cell proliferation by upregulating miRNA-487a. Cell Mol Biol Lett. 2019; 24:26. PMC: 6449898. DOI: 10.1186/s11658-019-0148-y. View

McGlynn K, Petrick J, El-Serag H . Epidemiology of Hepatocellular Carcinoma. Hepatology. 2020; 73 Suppl 1:4-13. PMC: 7577946. DOI: 10.1002/hep.31288. View

Sun H, Yang B, Zhang H, Song J, Zhang Y, Xing J . RRM2 is a potential prognostic biomarker with functional significance in glioma. Int J Biol Sci. 2019; 15(3):533-543. PMC: 6367584. DOI: 10.7150/ijbs.30114. View

Yang P, Lin L, Liu T . Sorafenib Inhibits Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in Hepatocellular Carcinoma Cells. Biomolecules. 2020; 10(1). PMC: 7022495. DOI: 10.3390/biom10010117. View

Shu Z, Li Z, Huang H, Chen Y, Fan J, Yu L . Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition. Oncogene. 2020; 39(35):5721-5733. DOI: 10.1038/s41388-020-01403-y. View

Nordlund P, Reichard P . Ribonucleotide reductases. Annu Rev Biochem. 2006; 75:681-706. DOI: 10.1146/annurev.biochem.75.103004.142443. View

10.

Li S, Peng F, Ning Y, Jiang P, Peng J, Ding X . SNHG16 as the miRNA let-7b-5p sponge facilitates the G2/M and epithelial-mesenchymal transition by regulating CDC25B and HMGA2 expression in hepatocellular carcinoma. J Cell Biochem. 2019; 121(3):2543-2558. DOI: 10.1002/jcb.29477. View

11.

Li Z, Shu Y, Chen C, Li X, Li M, Zhao X . Acquired tamoxifen resistance is surmounted by GW8510 through ribonucleotide reductase M2 downregulation-mediated autophagy induction. Biochem Biophys Res Commun. 2020; 528(3):554-560. DOI: 10.1016/j.bbrc.2020.05.149. View

12.

Sharma P, Allison J . The future of immune checkpoint therapy. Science. 2015; 348(6230):56-61. DOI: 10.1126/science.aaa8172. View

13.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

14.

Gandhi M, Gross M, Holler J, Coggins S, Patil N, Leupold J . The lncRNA lincNMR regulates nucleotide metabolism via a YBX1 - RRM2 axis in cancer. Nat Commun. 2020; 11(1):3214. PMC: 7316977. DOI: 10.1038/s41467-020-17007-9. View

15.

Mazzu Y, Armenia J, Chakraborty G, Yoshikawa Y, Coggins S, Nandakumar S . A Novel Mechanism Driving Poor-Prognosis Prostate Cancer: Overexpression of the DNA Repair Gene, Ribonucleotide Reductase Small Subunit M2 (RRM2). Clin Cancer Res. 2019; 25(14):4480-4492. PMC: 6820162. DOI: 10.1158/1078-0432.CCR-18-4046. View

16.

Shen X, Ding Y, Lu F, Yuan H, Luan W . Long noncoding RNA MIR4435-2HG promotes hepatocellular carcinoma proliferation and metastasis through the miR-22-3p/YWHAZ axis. Am J Transl Res. 2020; 12(10):6381-6394. PMC: 7653602. View

17.

Chen P, Wu J, Shu Y, Jiang H, Zhao X, Qian H . Gemcitabine resistance mediated by ribonucleotide reductase M2 in lung squamous cell carcinoma is reversed by GW8510 through autophagy induction. Clin Sci (Lond). 2018; 132(13):1417-1433. DOI: 10.1042/CS20180010. View

18.

Petitprez F, Meylan M, De Reynies A, Sautes-Fridman C, Fridman W . The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies. Front Immunol. 2020; 11:784. PMC: 7221158. DOI: 10.3389/fimmu.2020.00784. View

19.

Yang X, Cheng T, He Q, Lei Z, Chi J, Tang Z . LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway. Mol Cancer. 2018; 17(1):126. PMC: 6106894. DOI: 10.1186/s12943-018-0874-1. View

20.

Coussens L, Zitvogel L, Palucka A . Neutralizing tumor-promoting chronic inflammation: a magic bullet?. Science. 2013; 339(6117):286-91. PMC: 3591506. DOI: 10.1126/science.1232227. View