Lei Da, Wang Tao
Department of Hepatopancreatobiliary and Spleen Surgery, Baoji Central Hospital, Baoji 721008, Shannxi Province, China.
J Oncol. 2022 Mar 19;2022:2659563. doi: 10.1155/2022/2659563. eCollection 2022.
Circular RNAs (circRNAs) and microRNAs are crucial for progressing of hepatocellular carcinoma (HCC). Nonetheless, the function or mechanisms of a newly discovered circRNA, circSYPL1, as well as miR-506-3p, in the progression of HCC are mostly unexplained. The purpose of this research was to determine the mechanisms by which circSYPL1 and miR-506-3p regulate the malignant features of HCC.
The expression level of circSYPL1 was indeed detected using real-time PCR in HCC cell lines, primary as well as metastatic cancers. To assess the functionality of circSYPL1 upregulation and knockdown, we used proliferation and apoptosis, in addition to migration assays, as well as tumor xenograft and lung metastasis assays. The mechanisms of competing endogenous RNAs with circSYPL1/miR-506-3p/EZH2 were investigated using luciferase as well as RNA pull-down experiments. Lastly, cell proliferation and migration, in addition to tumor xenograft tests, were used to validate the biological significance of the circSYPL1/miR-506-3p/EZH2 signaling axis through overexpression or otherwise silencing.
circSYPL1 expression was significantly upregulated in HCC cell lines, in addition to primary and metastatic tumors of patients with HCC. Additionally, it may promote HCC initiation, development as well as progression. By knocking down circSYPL1 siRNA, we were able to drastically decrease the aggressiveness of HCC cells. circSYPL1 sponged miR-506-3p to boost EZH2 expression levels, as indicated by luciferase and RNA pull-down assays. Furthermore, circSYPL1 overexpression could upregulate EZH2 expression, while miR-506-3p mimics or EZH2 shRNAs could reverse the circSYPL1-induced malignancy of HCC cells.
On a mechanistic level, circSYPL1 can interact with miR-506-3p in a competitive manner to upregulate EZH2, hence increasing the aggressiveness of tumors.
环状RNA（circRNAs）和微小RNA对肝细胞癌（HCC）的进展至关重要。然而，新发现的circRNA circSYPL1以及miR-506-3p在HCC进展中的功能或机制大多尚不清楚。本研究的目的是确定circSYPL1和miR-506-3p调节HCC恶性特征的机制。
使用实时PCR在HCC细胞系、原发性和转移性癌中检测circSYPL1的表达水平。为了评估circSYPL1上调和敲低的功能，我们除了进行迁移试验外，还使用了增殖和凋亡试验，以及肿瘤异种移植和肺转移试验。使用荧光素酶和RNA下拉实验研究circSYPL1/miR-506-3p/EZH2竞争性内源RNA的机制。最后，通过过表达或沉默来验证circSYPL1/miR-506-3p/EZH2信号轴的生物学意义，包括细胞增殖和迁移以及肿瘤异种移植试验。
circSYPL1在HCC细胞系以及HCC患者的原发性和转移性肿瘤中表达显著上调。此外，它可能促进HCC的起始、发展以及进展。通过敲低circSYPL1 siRNA，我们能够大幅降低HCC细胞的侵袭性。荧光素酶和RNA下拉试验表明，circSYPL1通过海绵吸附miR-506-3p来提高EZH2表达水平。此外，circSYPL1过表达可上调EZH2表达，而miR-506-3p模拟物或EZH2 shRNAs可逆转circSYPL1诱导的HCC细胞恶性程度。
在机制层面上，circSYPL1可以与miR-506-3p竞争性相互作用以上调EZH2，从而增加肿瘤的侵袭性。
