Shu Meng-Lu, Yang Wan-Ting, Li Hui-Min, Qian Cui-Juan, Teng Xiao-Sheng, Yao Jun
Early Gastrointestinal Cancer Research Center, Taizhou Central Hospital (Taizhou University Hospital), School of Medicine, Taizhou University, Taizhou, 318000, Zhejiang Province, China.
Department of Gastroenterology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, 318000, Zhejiang Province, China.
Discov Oncol. 2024 Nov 18;15(1):670. doi: 10.1007/s12672-024-01550-8.
Both lipid metabolism and cyclic RNAs (circRNAs) have been found to be involved in pancreatic adenocarcinoma (PAAD) progression, but the relationship between lipid metabolism and circRNAs remains unclear.
The expression levels of miR-223-3p, circ_0124346, and acyl-CoA synthetase long chain family member 3 (ACSL3) were determined through qRT-PCR and Western blot analysis. Cell proliferation was evaluated using the CCK-8 and EdU incorporation assays. Cholesterol (CH) and triglyceride (TG) levels were quantified using relevant kits. The relationships between miR-223-3p and circ_0124346 or ACSL3 mRNA were examined by bioinformatics analysis, luciferase reporter, RNA-RNA pull-down, and RIP assays.
We observed a significant elevation in circ_0124346 expression in both pancreatic adenocarcinoma (PAAD) tissues and cell lines, and its expression level was shown to be correlated with tumor size. Circ_0124346 stimulated cell proliferation and facilitated lipid synthesis in PAAD cells. Additionally, we found that circ_0124346 functioned as a sponge for miR-223-3p, preventing miR-223-3p's binding to the 3'-UTR of ACSL3 mRNA, which subsequently led to an elevation in ACSL3 expression and promoted lipid synthesis. Accordingly, circ_0124346 knockdown resulted in a significant decrease in lipid synthesis and cell proliferation in PAAD cells, with partial reversal of these effects achieved via inhibiting miR-223-3p or overexpressing ACSL3.
Our study demonstrated that circ_0124346 regulates lipid metabolism in PAAD cells via the miR-223-3p/ACSL3 axis, suggesting that targeting circ_0124346 may serve as a potential strategy for treating PAAD and assisting in its diagnosis.
脂质代谢和环状RNA（circRNAs）均被发现参与胰腺腺癌（PAAD）的进展，但脂质代谢与circRNAs之间的关系仍不清楚。
通过qRT-PCR和蛋白质免疫印迹分析确定miR-223-3p、circ_0124346和酰基辅酶A合成酶长链家族成员3（ACSL3）的表达水平。使用CCK-8和EdU掺入试验评估细胞增殖。使用相关试剂盒定量胆固醇（CH）和甘油三酯（TG）水平。通过生物信息学分析、荧光素酶报告基因、RNA-RNA下拉和RIP试验研究miR-223-3p与circ_0124346或ACSL3 mRNA之间的关系。
我们观察到胰腺腺癌（PAAD）组织和细胞系中circ_0124346表达显著升高，且其表达水平与肿瘤大小相关。Circ_0124346刺激PAAD细胞的增殖并促进脂质合成。此外，我们发现circ_0124346作为miR-223-3p的海绵，阻止miR-223-3p与ACSL3 mRNA的3'-UTR结合，随后导致ACSL3表达升高并促进脂质合成。因此，circ_0124346敲低导致PAAD细胞中脂质合成和细胞增殖显著降低，通过抑制miR-223-3p或过表达ACSL3可部分逆转这些作用。
我们的研究表明，circ_0124346通过miR-223-3p/ACSL3轴调节PAAD细胞中的脂质代谢，提示靶向circ_0124346可能作为治疗PAAD和辅助其诊断的潜在策略。
