Xue Cailin, Zhang Xudong, Gao Peng, Cui Xiaohan, Zhu Chunfu, Qin Xihu
Department of Hepatobiliary Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, P.R. China.
Nanjing Medical University, Nanjing, Jiangsu, 211166, P.R. China.
J Cancer. 2021 Jan 1;12(4):1061-1072. doi: 10.7150/jca.52413. eCollection 2021.
Hepatocellular carcinoma (HCC), a most common malignant tumor, has an unfavorable clinical outcome. Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) play an important role in the carcinogenesis and progression of HCC. However, the clinical significances and the biological roles of most lncRNAs in HCC remain poorly understood. The expression levels of lncRNA loc339803 in HCC tissues and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The cellular sublocalization of loc339803 was determined by fluorescence hybridization and nuclear and cytoplasmic RNA isolation assay. Western blot, CCK-8, Edu, colony formation, migration and invasion assays were used to investigate the roles of loc339803 in HCC progression . A mouse model for lung metastasis was constructed to evaluate the role of loc339803 in HCC development . The correlations among loc339803, miR-30a-5p and SNAIL1 were validated by qRT-PCR and a dual- luciferase reporter assay. The expression of loc339803 was upregulated in HCC tissues and cell lines, and positively correlated with tumor size, advanced tumor stage, higher serum AFP level and poor prognosis of HCC patients. Loc339803 can promote the migration and invasion of HCC cells and . Further studies demonstrated that loc339803 functioned as a competing endogenous RNA (ceRNA) by directly binding to miR-30a-5p, thus up-regulating the expression of SNAIL1, a target gene of miR-30a-5p. Moreover, miR-30a-5p upregulation blocked the enhanced migration and invasion of HCC cells induced by loc339803 overexpression. Loc339803 may be oncogenic in HCC and associated with poor clinical outcomes. LncRNA loc339803 might promote the invasion and migration of HCC cells through regulating miR-30a-5p/ SNAIL1 axis.
肝细胞癌（HCC）是最常见的恶性肿瘤，临床预后不佳。新出现的证据表明，长链非编码RNA（lncRNA）在HCC的发生和发展中起重要作用。然而，大多数lncRNA在HCC中的临床意义和生物学作用仍知之甚少。通过定量实时聚合酶链反应（qRT-PCR）检测法测定lncRNA loc339803在HCC组织和细胞系中的表达水平。通过荧光杂交以及细胞核和细胞质RNA分离检测法确定loc339803的细胞亚定位。采用蛋白质免疫印迹法、CCK-8法、Edu法、集落形成法、迁移和侵袭检测法研究loc339803在HCC进展中的作用。构建肺转移小鼠模型以评估loc339803在HCC发展中的作用。通过qRT-PCR和双荧光素酶报告基因检测法验证loc339803、miR-30a-5p和SNAIL1之间的相关性。loc339803在HCC组织和细胞系中表达上调，且与肿瘤大小、肿瘤晚期、血清甲胎蛋白水平升高以及HCC患者的不良预后呈正相关。Loc339803可促进HCC细胞的迁移和侵袭。进一步研究表明，loc339803通过直接结合miR-30a-5p发挥竞争性内源RNA（ceRNA）的功能，从而上调miR-30a-5p的靶基因SNAIL1的表达。此外，miR-30a-5p上调可阻断由loc339803过表达诱导的HCC细胞迁移和侵袭增强。Loc339803在HCC中可能具有致癌性，并与不良临床结局相关。LncRNA loc339803可能通过调节miR-30a-5p/SNAIL1轴促进HCC细胞的侵袭和迁移。
