Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in Preclinical Models

Overview

Journal Cancer Genomics Proteomics

Specialties Biochemistry
Genetics
Oncology

Date 2023 Oct 27

PMID 37889063

Authors

Ulrich H Weidle

Adam Nopora

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) ranges as number two with respect to the incidence of tumors and is associated with a dismal prognosis. The therapeutic efficacy of approved multi-tyrosine kinase inhibitors and checkpoint inhibitors is modest. Therefore, the identification of new therapeutic targets and entities is of paramount importance. We searched the literature for up-regulated circular RNAs (circRNAs) which mediate efficacy in preclinical in vivo models of HCC. Our search resulted in 14 circRNAs which up-regulate plasma membrane transmembrane receptors, while 5 circRNAs induced secreted proteins. Two circRNAs facilitated replication of Hepatitis B or C viruses. Three circRNAs up-regulated high mobility group proteins. Six circRNAs regulated components of the ubiquitin system. Seven circRNAs induced GTPases of the family of ras-associated binding proteins (RABs). Three circRNAs induced redox-related proteins, eight of them up-regulated metabolic enzymes and nine circRNAs induced signaling-related proteins. The identified circRNAs up-regulate the corresponding targets by sponging microRNAs. Identified circRNAs and their targets have to be validated by standard criteria of preclinical drug development. Identified targets can potentially be inhibited by small molecules or antibody-based moieties and circRNAs can be inhibited by small-interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) for therapeutic purposes.

References

Li S, Weng J, Song F, Li L, Xiao C, Yang W . Circular RNA circZNF566 promotes hepatocellular carcinoma progression by sponging miR-4738-3p and regulating TDO2 expression. Cell Death Dis. 2020; 11(6):452. PMC: 7293356. DOI: 10.1038/s41419-020-2616-8. View

Shen D, Zhao H, Zeng P, Ge M, Shrestha S, Zhao W . Circular RNA circ_0001459 accelerates hepatocellular carcinoma progression via the miR-6165/IGF1R axis. Ann N Y Acad Sci. 2022; 1512(1):46-60. PMC: 9306989. DOI: 10.1111/nyas.14753. View

Huang A, Yang X, Chung W, Dennison A, Zhou J . Targeted therapy for hepatocellular carcinoma. Signal Transduct Target Ther. 2020; 5(1):146. PMC: 7419547. DOI: 10.1038/s41392-020-00264-x. View

Zheng N, Wei W, Wang Z . Emerging roles of FGF signaling in hepatocellular carcinoma. Transl Cancer Res. 2016; 5(1):1-6. PMC: 4876964. View

Nishikawa H, Koyama S . Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies. J Immunother Cancer. 2021; 9(7). PMC: 8327843. DOI: 10.1136/jitc-2021-002591. View

Simpson J, Griffiths G, Wessling-Resnick M, Fransen J, Bennett H, Jones A . A role for the small GTPase Rab21 in the early endocytic pathway. J Cell Sci. 2004; 117(Pt 26):6297-311. DOI: 10.1242/jcs.01560. View

Shigesawa T, Maehara O, Suda G, Natsuizaka M, Kimura M, Shimazaki T . Lenvatinib suppresses cancer stem-like cells in HCC by inhibiting FGFR1-3 signaling, but not FGFR4 signaling. Carcinogenesis. 2020; 42(1):58-69. DOI: 10.1093/carcin/bgaa049. View

Imoto I, Pimkhaokham A, Watanabe T, Soeda E, Inazawa J . Amplification and overexpression of TGIF2, a novel homeobox gene of the TALE superclass, in ovarian cancer cell lines. Biochem Biophys Res Commun. 2000; 276(1):264-70. DOI: 10.1006/bbrc.2000.3449. View

Notas G, Alexaki V, Kampa M, Pelekanou V, Charalampopoulos I, Sabour-Alaoui S . APRIL binding to BCMA activates a JNK2-FOXO3-GADD45 pathway and induces a G2/M cell growth arrest in liver cells. J Immunol. 2012; 189(10):4748-58. DOI: 10.4049/jimmunol.1102891. View

10.

Wang Y, Liu D, Zhang T, Xia L . FGF/FGFR Signaling in Hepatocellular Carcinoma: From Carcinogenesis to Recent Therapeutic Intervention. Cancers (Basel). 2021; 13(6). PMC: 8002748. DOI: 10.3390/cancers13061360. View

11.

Corvaia N, Beck A, Caussanel V, Goetsch L . Insulin-like growth factor receptor type I as a target for cancer therapy. Front Biosci (Schol Ed). 2013; 5(2):439-50. DOI: 10.2741/s382. View

12.

Liu Y, Wang L, Liu W . Roles of circRNAs in the Tumorigenesis and Metastasis of HCC: A Mini Review. Cancer Manag Res. 2022; 14:1847-1856. PMC: 9166687. DOI: 10.2147/CMAR.S362594. View

13.

Wu F, Li T, Su S, Yu J, Zhang H, Tan G . STC2 as a novel mediator for Mus81-dependent proliferation and survival in hepatocellular carcinoma. Cancer Lett. 2016; 388:177-186. DOI: 10.1016/j.canlet.2016.11.039. View

14.

Zogg H, Singh R, Ro S . Current Advances in RNA Therapeutics for Human Diseases. Int J Mol Sci. 2022; 23(5). PMC: 8911101. DOI: 10.3390/ijms23052736. View

15.

Antimisiaris S, Mourtas S, Papadia K . Targeted si-RNA with liposomes and exosomes (extracellular vesicles): How to unlock the potential. Int J Pharm. 2017; 525(2):293-312. DOI: 10.1016/j.ijpharm.2017.01.056. View

16.

Peng R, Zhang P, Yang X, Wei C, Huang X, Cai J . Overexpression of RNF38 facilitates TGF-β signaling by Ubiquitinating and degrading AHNAK in hepatocellular carcinoma. J Exp Clin Cancer Res. 2019; 38(1):113. PMC: 6402116. DOI: 10.1186/s13046-019-1113-3. View

17.

Zhang T, Zhang L, Han D, Tursun K, Lu X . Circular RNA hsa_Circ_101141 as a Competing Endogenous RNA Facilitates Tumorigenesis of Hepatocellular Carcinoma by Regulating miR-1297/ROCK1 Pathway. Cell Transplant. 2020; 29:963689720948016. PMC: 7563807. DOI: 10.1177/0963689720948016. View

18.

Xue J, Suarez J, Minaai M, Li S, Gaudino G, Pass H . HMGB1 as a therapeutic target in disease. J Cell Physiol. 2020; 236(5):3406-3419. PMC: 8104204. DOI: 10.1002/jcp.30125. View

19.

Xu Y, Guo Q, Wei L . The Emerging Influences of Alpha-Fetoprotein in the Tumorigenesis and Progression of Hepatocellular Carcinoma. Cancers (Basel). 2021; 13(20). PMC: 8534193. DOI: 10.3390/cancers13205096. View

20.

Liu J, He X, Zou Y, Wang K . Circular RNA Circ-STIL Contributes to Cell Growth and Metastasis in Hepatocellular Carcinoma via Regulating miR-345-5p/AQP3 Axis. Dig Dis Sci. 2021; 67(6):2269-2282. DOI: 10.1007/s10620-021-07054-7. View