New Axes of Interaction in Circ_0079593/miR-516b-5p Network in Melanoma Metastasis Cell Lines

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2025 Jan 8

PMID 39766913

Authors

Elisa De Tomi

Elisa Orlandi

Francesca Belpinati

Cristina Patuzzo

Elisabetta Trabetti

Macarena Gomez-Lira

Giovanni Malerba

Affiliations

Soon will be listed here.

Abstract

Background/objectives: microRNAs (miRNAs) and circular RNA (circRNAs) show a close interconnection in the control of fundamental functions, such as cell proliferation and tumor development. A full understanding of this complex and interconnected network is essential for better understanding the mechanisms underlying cancer progression. Hsa_circ_0079593 is a circRNA highly expressed in melanoma and is associated with increased metastasis and progression of malignancy, whereas miR516b-5p is a microRNA whose expression is lower in several tumor types, including melanoma; its overexpression inhibits cell proliferation, migration, and invasion. In this study, we tested whether circ_0079593 is involved in the progression of melanoma aggressiveness by regulating CHAF1B and MCAM via the inhibition of miR-516b-5p.

Methods: We first verified the expression of the key components in both healthy melanocyte lines and melanoma metastases, subsequently using in vitro assays such as scratch tests, Western blot, qRT-PCR, and dual luciferase report assay; we verified their interconnected regulatory effect.

Results: Our results showed that circ_0079593-miR516b-5p interactions are involved in the increase in the migration of metastasis melanoma cells by exploiting their binding to MCAM and CHAF1B mRNAs.

Conclusions: This study provides two other regulatory networks in which circ_0079593 may exert its oncogenic function by increasing the speed of movement of metastatic cells through the sponge of miR-516b-5p, which cannot regulate MCAM and CHAF1B expression.

References

Piwecka M, Glazar P, Hernandez-Miranda L, Memczak S, Wolf S, Rybak-Wolf A . Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 2017; 357(6357). DOI: 10.1126/science.aam8526. View

Lazar A, Dinescu S, Costache M . The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy. Cancers (Basel). 2020; 12(11). PMC: 7696690. DOI: 10.3390/cancers12113378. View

Ruiter D, Spatz A, van den Oord J, Cook M . Pathologic staging of melanoma. Semin Oncol. 2002; 29(4):370-81. DOI: 10.1053/sonc.2002.34116. View

Smolarz B, Durczynski A, Romanowicz H, Szyllo K, Hogendorf P . miRNAs in Cancer (Review of Literature). Int J Mol Sci. 2022; 23(5). PMC: 8910953. DOI: 10.3390/ijms23052805. View

Xu Y, Jiang T, Wu C, Zhang Y . CircAKT3 inhibits glycolysis balance in lung cancer cells by regulating miR-516b-5p/STAT3 to inhibit cisplatin sensitivity. Biotechnol Lett. 2020; 42(7):1123-1135. DOI: 10.1007/s10529-020-02846-9. View

Svoronos A, Engelman D, Slack F . OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer. Cancer Res. 2016; 76(13):3666-70. PMC: 4930690. DOI: 10.1158/0008-5472.CAN-16-0359. View

Hao Y, Wang X . Circ-0079593 promotes proliferation and migration of melanoma cells by sponging microRNA-433 and elevating EGFR expression. Eur Rev Med Pharmacol Sci. 2021; 25(2):779-786. DOI: 10.26355/eurrev_202101_24639. View

Wang X, Cheng Q . Suppression of exosomal hsa_circ_0001005 eliminates the Vemurafenib resistance of melanoma. J Cancer Res Clin Oncol. 2023; 149(9):5921-5936. DOI: 10.1007/s00432-022-04434-y. View

Wang Q, Chen J, Wang A, Sun L, Qian L, Zhou X . Differentially expressed circRNAs in melanocytes and melanoma cells and their effect on cell proliferation and invasion. Oncol Rep. 2018; 39(4):1813-1824. DOI: 10.3892/or.2018.6263. View

10.

Mercer T, Dinger M, Mattick J . Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009; 10(3):155-9. DOI: 10.1038/nrg2521. View

11.

Frias-Lasserre D, Villagra C . The Importance of ncRNAs as Epigenetic Mechanisms in Phenotypic Variation and Organic Evolution. Front Microbiol. 2018; 8:2483. PMC: 5744636. DOI: 10.3389/fmicb.2017.02483. View

12.

Zhang X, Xie K, Zhou H, Wu Y, Li C, Liu Y . Role of non-coding RNAs and RNA modifiers in cancer therapy resistance. Mol Cancer. 2020; 19(1):47. PMC: 7050132. DOI: 10.1186/s12943-020-01171-z. View

13.

Kristensen L, Hansen T, Veno M, Kjems J . Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2017; 37(5):555-565. PMC: 5799710. DOI: 10.1038/onc.2017.361. View

14.

Daniotti M, Oggionni M, Ranzani T, Vallacchi V, Campi V, Di Stasi D . BRAF alterations are associated with complex mutational profiles in malignant melanoma. Oncogene. 2004; 23(35):5968-77. DOI: 10.1038/sj.onc.1207780. View

15.

Xiao M, Ai Y, Wilusz J . Biogenesis and Functions of Circular RNAs Come into Focus. Trends Cell Biol. 2020; 30(3):226-240. PMC: 7069689. DOI: 10.1016/j.tcb.2019.12.004. View

16.

Liang Z, Guo C, Zou M, Meng P, Zhang T . circRNA-miRNA-mRNA regulatory network in human lung cancer: an update. Cancer Cell Int. 2020; 20:173. PMC: 7236303. DOI: 10.1186/s12935-020-01245-4. View

17.

Pang Y, Maxwell E, Sindrewicz-Goral P, Shapanis A, Li S, Morgan M . Galectin-3 Is a Natural Binding Ligand of MCAM (CD146, MUC18) in Melanoma Cells and Their Interaction Promotes Melanoma Progression. Biomolecules. 2022; 12(10). PMC: 9599063. DOI: 10.3390/biom12101451. View

18.

Rapanotti M, Cugini E, Nuccetelli M, Terrinoni A, Di Raimondo C, Lombardo P . MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy. Int J Mol Sci. 2021; 22(22). PMC: 8623757. DOI: 10.3390/ijms222212416. View

19.

Lei X, Guan C, Song Y, Wang H . The multifaceted role of CD146/MCAM in the promotion of melanoma progression. Cancer Cell Int. 2015; 15(1):3. PMC: 4326486. DOI: 10.1186/s12935-014-0147-z. View

20.

Lu M, Wu Y, Zeng B, Sun J, Li Y, Luo J . CircEHMT1 inhibits metastatic potential of breast cancer cells by modulating miR-1233-3p/KLF4/MMP2 axis. Biochem Biophys Res Commun. 2020; 526(2):306-313. DOI: 10.1016/j.bbrc.2020.03.084. View