De Tomi Elisa, Orlandi Elisa, Belpinati Francesca, Patuzzo Cristina, Trabetti Elisabetta, Gomez-Lira Macarena, Malerba Giovanni
Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, 37134 Verona, Italy.
Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37134 Verona, Italy.
Genes (Basel). 2024 Dec 21;15(12):1647. doi: 10.3390/genes15121647.
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.
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.
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.
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.
背景/目的:微小RNA(miRNA)和环状RNA(circRNA)在细胞增殖和肿瘤发展等基本功能的调控中显示出密切的相互联系。全面了解这个复杂且相互关联的网络对于更好地理解癌症进展的潜在机制至关重要。Hsa_circ_0079593是一种在黑色素瘤中高表达的circRNA,与恶性肿瘤转移和进展的增加相关,而miR516b - 5p是一种微小RNA,其在包括黑色素瘤在内的几种肿瘤类型中的表达较低;其过表达可抑制细胞增殖、迁移和侵袭。在本研究中,我们测试了circ_0079593是否通过抑制miR - 516b - 5p来调节CHAF1B和MCAM从而参与黑色素瘤侵袭性的进展。
我们首先在健康黑素细胞系和黑色素瘤转移灶中验证关键成分的表达,随后使用划痕试验、蛋白质印迹、qRT - PCR和双荧光素酶报告基因检测等体外实验;我们验证了它们之间相互的调节作用。
我们的结果表明,circ_0079593 - miR516b - 5p相互作用通过与MCAM和CHAF1B mRNA结合参与转移性黑色素瘤细胞迁移的增加。
本研究提供了另外两个调控网络,其中circ_0079593可能通过miR - 516b - 5p海绵体增加转移细胞的移动速度来发挥其致癌功能,而miR - 516b - 5p无法调节MCAM和CHAF1B的表达。