Feng Kun-Liang, Diao Na, Zhou Zhai-Wen, Fang Chong-Kai, Wang Ji-Nan, Zhang Ying, Luo Rui, Zhong Chong
Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Cell Dev Biol. 2022 May 3;10:850708. doi: 10.3389/fcell.2022.850708. eCollection 2022.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Circular RNAs (circRNAs) play critical roles in the progression of HCC. However, the role of the newly identified circFGGY (hsa_circ_0006633) in the development and progression of HCC has not been explored. In this study, we found that circFGGY was significantly downregulated in tumor compared with that in adjacent normal liver tissues of patients with HCC. HCC patients with low circFGGY expression had poor overall survival after hepatectomy. Moreover, it was found that circFGGY could inhibit the proliferation, invasion and epithelial-mesenchymal transition of HCC both and . Mechanistically, circFGGY promoted the expression of Smad7, a well-known suppressor of the transforming growth factor-β signaling pathway. In addition, miR-545-3p, a tumor promoter targeting both circFGGY and Smad7, suppressed the upregulation of Smad7 caused by circFGGY overexpression. Collectively, our data revealed that circFGGY inhibits the proliferation and invasion of HCC cells by sponging miR-545-3p and promote the expression of Smad7, indicating that circFGGY functions as a tumor suppressor and could be a prognostic biomarker for HCC.
肝细胞癌(HCC)是全球癌症相关死亡的主要原因之一。环状RNA(circRNAs)在HCC进展中起关键作用。然而,新发现的circFGGY(hsa_circ_0006633)在HCC发生发展中的作用尚未得到研究。在本研究中,我们发现与HCC患者的癌旁正常肝组织相比,circFGGY在肿瘤组织中显著下调。circFGGY表达低的HCC患者肝切除术后总生存期较差。此外,发现circFGGY在体内和体外均可抑制HCC的增殖、侵袭及上皮-间质转化。机制上,circFGGY促进了转化生长因子-β信号通路的著名抑制因子Smad7的表达。此外,靶向circFGGY和Smad7的肿瘤促进因子miR-545-3p抑制了circFGGY过表达引起的Smad7上调。总之,我们的数据表明,circFGGY通过吸附miR-545-3p抑制HCC细胞的增殖和侵袭,并促进Smad7的表达,表明circFGGY作为一种肿瘤抑制因子,可能是HCC的一个预后生物标志物。