Li Jing, Han Ting, Li Zhenzhen, Han Hongmei, Yin Yingchun, Zhang Baohua, Zhang Hengming, Li Luan
Department of Pathology, Zibo Central Hospital, Zibo 255000, Shandong, China.
Department of Gastroenterology, Qilu Hospital of Shandong University (Qingdao), Qingdao 266035, Shandong, China.
J Oncol. 2022 Aug 27;2022:4184034. doi: 10.1155/2022/4184034. eCollection 2022.
Previous research studies have shown that the elevation of circular RNA (circRNA), hsa_circRNA_002178, was associated with the poor prognosis of breast cancer and colorectal cancer, while its molecular mechanisms underlying the effects on hepatocellular carcinoma (HCC) are still elusive.
The microarray dataset GSE97332 was obtained from the Gene Expression Omnibus (GEO) database and calculated by using the GEO2R tool to identify differentially expressed circRNAs. Differentially expressed hsa_circRNA_002178, in 7 HCC tissue samples and paracancerous tissues, as well as in HCC cell lines and normal hepatocytes, was checked by RT-qPCR. Cell proliferation, invasion, migration, and epithelial-to-mesenchymal transition (EMT)-related proteins were tested in hsa_circRNA_002178-overexpressed or hsa_circRNA_002178-knocked down HCC cells. Subsequently, we identified whether hsa_circRNA_002178 binds to serine- and arginine-rich splicing factor 1 (SRSF1) and then analyzed their function in regulating HCC cell behavior. The effect on HCC cell xenograft tumor growth was observed by the knockdown of hsa_circRNA_002178 .
GEO2R-based analysis displayed that hsa_circRNA_002178 was upregulated in HCC tissues. Overexpression or knockdown of hsa_circRNA_002178 encouraged or impeded HCC cell proliferation, migration, invasion, and EMT program. Mechanically, hsa_circRNA_002178 bound to SRSF1 3'-untranslated region (UTR) and stabilized its expression. SRSF1 weakening eliminated the effects of pcDNA-hsa_circRNA_002178 on cell malignant behavior. Finally, the knockdown of hsa_circRNA_002178 was confirmed to prevent xenograft tumor growth.
hsa_circRNA_002178 overexpression encouraged the stability of SRSF1 mRNA expression, and it may serve as an upstream factor of SRSF1 for the diagnosis of HCC.
先前的研究表明，环状RNA（circRNA）hsa_circRNA_002178的升高与乳腺癌和结直肠癌的不良预后相关，而其对肝细胞癌（HCC）影响的分子机制仍不清楚。
从基因表达综合数据库（GEO）获取微阵列数据集GSE97332，并使用GEO2R工具进行计算以鉴定差异表达的circRNA。通过RT-qPCR检测7例HCC组织样本、癌旁组织以及HCC细胞系和正常肝细胞中差异表达的hsa_circRNA_002178。在过表达或敲低hsa_circRNA_002178的HCC细胞中检测细胞增殖、侵袭、迁移以及上皮-间质转化（EMT）相关蛋白。随后，我们确定hsa_circRNA_002178是否与富含丝氨酸和精氨酸的剪接因子1（SRSF1）结合，然后分析它们在调节HCC细胞行为中的作用。通过敲低hsa_circRNA_002178观察其对HCC细胞异种移植瘤生长的影响。
基于GEO2R的分析显示hsa_circRNA_002178在HCC组织中上调。hsa_circRNA_002178的过表达或敲低促进或抑制了HCC细胞的增殖、迁移、侵袭和EMT进程。从机制上讲，hsa_circRNA_002178与SRSF1的3'-非翻译区（UTR）结合并稳定其表达。SRSF1的减弱消除了pcDNA-hsa_circRNA_002178对细胞恶性行为的影响。最后，证实敲低hsa_circRNA_002178可抑制异种移植瘤生长。
hsa_circRNA_002178的过表达促进了SRSF1 mRNA表达的稳定性，它可能作为SRSF1的上游因子用于HCC的诊断。
