Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, 530021, Nanning, Guangxi, China.
Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, 530021, Nanning, Guangxi, China.
Cancer Med. 2023 Jun;12(11):12553-12568. doi: 10.1002/cam4.5894. Epub 2023 Apr 11.
Many studies have shown that circular RNAs (circRNAs) are abnormally expressed in various tumor tissues and served as a key regulator in the occurrence and development of cancer. However, in hepatocellular carcinoma (HCC), the molecular mechanism of circRNAs in body fluids remains to be further explored.
The expression levels of genes and proteins were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Cell counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), wound healing assay, Transwell assays, flow cytometry, and tumor formation models in nude mice were conducted to investigate the effects of circFAM114A2 on HCC cells both in vitro and in vivo. RNA antisense purification (RAP), dual luciferase reporter assays and rescue assays were carried out to verify the interaction between circFAM114A2, miR-630 and HHIP.
CircFAM114A2 was significantly downregulated in HCC tissues and was associated with microvascular invasion and lymph node metastasis of HCC patients. We also observed that circFAM114A2 was lowly expressed in HCC plasma, which may serve as an effective biomarker to screen HCC patients from healthy controls (area under curve (AUC)=0.922). In vitro, circFAM114A2 overexpression significantly blunted HCC cell proliferation, migration, invasion, and promoted apoptosis, whereas circFAM114A2 silencing posed opposite effects. In vivo, circFAM114A2 overexpression inhibited the growth of HCC cells. Mechanistically, circFAM114A2 could increase the expression of the tumor suppressor HHIP via acting as a sponge for miR-630.
CircFAM114A2 exerts a tumor suppressor role in HCC through miR-630/HHIP axis, and may be served as a potential diagnostic and therapeutic biomarker for HCC patients.
许多研究表明，环状 RNA（circRNAs）在各种肿瘤组织中表达异常，作为癌症发生和发展的关键调节剂。然而，在肝细胞癌（HCC）中，体液中环状 RNA 的分子机制仍有待进一步探索。
通过定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹分别检测基因和蛋白质的表达水平。细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷（EdU）、划痕愈合试验、Transwell 测定、流式细胞术和裸鼠肿瘤形成模型用于研究 circFAM114A2 在体外和体内对 HCC 细胞的影响。RNA 反义纯化（RAP）、双荧光素酶报告基因测定和挽救测定用于验证 circFAM114A2、miR-630 和 HHIP 之间的相互作用。
circFAM114A2 在 HCC 组织中显著下调，与 HCC 患者的微血管侵犯和淋巴结转移有关。我们还观察到 HCC 血浆中 circFAM114A2 表达水平较低，可能作为从健康对照中筛选 HCC 患者的有效生物标志物（曲线下面积（AUC）=0.922）。在体外，circFAM114A2 过表达显著抑制 HCC 细胞增殖、迁移和侵袭，促进凋亡，而 circFAM114A2 沉默则产生相反的效果。在体内，circFAM114A2 过表达抑制 HCC 细胞的生长。机制上，circFAM114A2 通过作为 miR-630 的海绵来增加肿瘤抑制因子 HHIP 的表达。
circFAM114A2 通过 miR-630/HHIP 轴在 HCC 中发挥肿瘤抑制作用，可能作为 HCC 患者的潜在诊断和治疗生物标志物。
