MicroRNAs Involved in Metastasis of Hepatocellular Carcinoma: Target Candidates, Functionality and Efficacy in Animal Models and Prognostic Relevance

Overview

Journal Cancer Genomics Proteomics

Specialties Biochemistry
Genetics
Oncology

Date 2019 Dec 29

PMID 31882547

Citations 18

Authors

Ulrich H Weidle

Daniela Schmid

Fabian Birzele

Ulrich Brinkmann

Affiliations

Soon will be listed here.

Abstract

Hepatocellular carcinoma (HCC) is responsible for the second-leading cancer-related death toll worldwide. Although sorafenib and levantinib as frontline therapy and regorafenib, cabazantinib and ramicurimab have now been approved for second-line therapy, the therapeutic benefit is in the range of only a few months with respect to prolongation of survival. Aggressiveness of HCC is mediated by metastasis. Intrahepatic metastases and distant metastasis to the lungs, lymph nodes, bones, omentum, adrenal gland and brain have been observed. Therefore, the identification of metastasis-related new targets and treatment modalities is of paramount importance. In this review, we focus on metastasis-related microRNAs (miRs) as therapeutic targets for HCC. We describe miRs which mediate or repress HCC metastasis in mouse xenograft models. We discuss 18 metastasis-promoting miRs and 35 metastasis-inhibiting miRs according to the criteria as outlined. Six of the metastasis-promoting miRs (miR-29a, -219-5p, -331-3p, 425-5p, -487a and -1247-3p) are associated with unfavourable clinical prognosis. Another set of six down-regulated miRs (miR-101, -129-3p, -137, -149, -503, and -630) correlate with a worse clinical prognosis. We discuss the corresponding metastasis-related targets as well as their potential as therapeutic modalities for treatment of HCC-related metastasis. A subset of up-regulated miRs -29a, -219-5p and -425-5p and down-regulated miRs -129-3p and -630 were evaluated in orthotopic metastasis-related models which are suitable to mimic HCC-related metastasis. Those miRNAs may represent prioritized targets emerging from our survey.

Citing Articles

MicroRNAs and RNA-Binding Protein-Based Regulation of Bone Metastasis from Hepatobiliary Cancers and Potential Therapeutic Strategies.

Fagoonee S, Weiskirchen R Cells. 2024; 13(23).

PMID: 39682684 PMC: 11640337. DOI: 10.3390/cells13231935.

Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications.

Romeo M, Dallio M, Scognamiglio F, Ventriglia L, Cipullo M, Coppola A Cancers (Basel). 2023; 15(21).

PMID: 37958352 PMC: 10647270. DOI: 10.3390/cancers15215178.

MicroRNA-188-5p inhibits hepatocellular carcinoma proliferation and migration by targeting forkhead box N2.

Wu Y, Yu B, Zhou J, Shen X, Chen W, Ai X BMC Cancer. 2023; 23(1):511.

PMID: 37277714 PMC: 10243064. DOI: 10.1186/s12885-023-10901-7.

Exosomes loaded with miR-665 inhibit the progression of osteosarcoma and .

Zhang B, Yang Y, Tao R, Yao C, Zhou Z, Zhang Y Am J Transl Res. 2022; 14(10):7012-7026.

PMID: 36398229 PMC: 9641455.

Bladder Cancer-related microRNAs With In Vivo Efficacy in Preclinical Models.

Weidle U, Birzele F Cancer Diagn Progn. 2022; 1(4):245-263.

PMID: 35403137 PMC: 8988954. DOI: 10.21873/cdp.10033.

References

Tsai W, Hsu P, Lai T, Chau G, Lin C, Chen C . MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009; 49(5):1571-82. DOI: 10.1002/hep.22806. View

Cimmino A, Calin G, Fabbri M, Iorio M, Ferracin M, Shimizu M . miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005; 102(39):13944-9. PMC: 1236577. DOI: 10.1073/pnas.0506654102. View

Yuen M, Wu P, Lai V, Lau J, Lai C . Expression of c-Myc, c-Fos, and c-jun in hepatocellular carcinoma. Cancer. 2001; 91(1):106-12. DOI: 10.1002/1097-0142(20010101)91:1<106::aid-cncr14>3.0.co;2-2. View

Kim C, Lee H, Gupta N, Ramachandran S, Kaushik I, Srivastava S . Role of Forkhead Box Class O proteins in cancer progression and metastasis. Semin Cancer Biol. 2017; 50:142-151. PMC: 5794649. DOI: 10.1016/j.semcancer.2017.07.007. View

Black R, Rauch C, Kozlosky C, Peschon J, Slack J, Wolfson M . A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature. 1997; 385(6618):729-33. DOI: 10.1038/385729a0. View

Zhu W, Qin L . GOLM1-regulated EGFR/RTK recycling is a novel target for combating HCC metastasis. Sci China Life Sci. 2016; 60(1):98-101. DOI: 10.1007/s11427-016-0311-x. View

Chen C, Wang S, Liu C, Wu Y, Wang W, Huang J . β-1,4-Galactosyltransferase III suppresses β1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer. Carcinogenesis. 2014; 35(6):1258-66. DOI: 10.1093/carcin/bgu007. View

Wang R, Wang J, Chu X, Geng H, Chen L . Expression of STK15 mRNA in hepatocellular carcinoma and its prognostic significance. Clin Biochem. 2009; 42(7-8):641-7. DOI: 10.1016/j.clinbiochem.2009.01.023. View

Felici A, Giubellino A, Bottaro D . Gab1 mediates hepatocyte growth factor-stimulated mitogenicity and morphogenesis in multipotent myeloid cells. J Cell Biochem. 2010; 111(2):310-21. PMC: 3393599. DOI: 10.1002/jcb.22695. View

10.

Bazzoni G, Dejana E . Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev. 2004; 84(3):869-901. DOI: 10.1152/physrev.00035.2003. View

11.

Llovet J, Montal R, Sia D, Finn R . Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 2018; 15(10):599-616. DOI: 10.1038/s41571-018-0073-4. View

12.

Gao S, Zheng Q, Xu B, Pan C, Li K, Zhao Y . EZH2 represses target genes through H3K27-dependent and H3K27-independent mechanisms in hepatocellular carcinoma. Mol Cancer Res. 2014; 12(10):1388-97. DOI: 10.1158/1541-7786.MCR-14-0034. View

13.

Chang R, Xu J, Fang F, Yang H, Yang L . MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling. Tumour Biol. 2016; 37(8):10609-19. DOI: 10.1007/s13277-016-4919-z. View

14.

Katyal S, Oliver 3rd J, Peterson M, Ferris J, Carr B, BARON R . Extrahepatic metastases of hepatocellular carcinoma. Radiology. 2000; 216(3):698-703. DOI: 10.1148/radiology.216.3.r00se24698. View

15.

Kornmann M, Ishiwata T, Beger H, Korc M . Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer: evidence for autocrine and paracrine actions. Oncogene. 1997; 15(12):1417-24. DOI: 10.1038/sj.onc.1201307. View

16.

Zhou H, Fang J, Shang L, Zhang Z, Sang Y, Xu L . MicroRNAs miR-125b and miR-100 suppress metastasis of hepatocellular carcinoma by disrupting the formation of vessels that encapsulate tumour clusters. J Pathol. 2016; 240(4):450-460. DOI: 10.1002/path.4804. View

17.

Zhang J, Yang Y, Yang T, Yuan S, Wang R, Pan Z . Double-negative feedback loop between microRNA-422a and forkhead box (FOX)G1/Q1/E1 regulates hepatocellular carcinoma tumor growth and metastasis. Hepatology. 2014; 61(2):561-73. DOI: 10.1002/hep.27491. View

18.

Luo C, Yin D, Zhan H, Borjigin U, Li C, Zhou Z . microRNA-501-3p suppresses metastasis and progression of hepatocellular carcinoma through targeting LIN7A. Cell Death Dis. 2018; 9(5):535. PMC: 5945677. DOI: 10.1038/s41419-018-0577-y. View

19.

Okazaki I, Inagaki Y . Novel strategies for hepatocellular carcinoma based on MMPs science. Anticancer Agents Med Chem. 2012; 12(7):753-63. DOI: 10.2174/187152012802650165. View

20.

Kim T, Vigil D, Der C, Juliano R . Role of DLC-1, a tumor suppressor protein with RhoGAP activity, in regulation of the cytoskeleton and cell motility. Cancer Metastasis Rev. 2009; 28(1-2):77-83. PMC: 2757774. DOI: 10.1007/s10555-008-9167-2. View