Yang Jing, Li Kun, Chen Jian, Hu Xiaoxiong, Wang He, Zhu Xuan
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Department of Gastroenterology and Hepatology, The People's Hospital of Yichun City, Yichun 336000, People's Republic of China.
Onco Targets Ther. 2020 Mar 6;13:1979-1991. doi: 10.2147/OTT.S239258. eCollection 2020.
Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. LINC00460, a novel long non-coding RNA (lncRNA), was recently confirmed as an oncogene in various cancers. However, the biological function and underlying mechanism of LINC00460 in HCC is largely obscure.
Fifty pairs of tumor tissue and adjacent normal tissues from HCC patients, as well as six HCC cell lines and a normal human hepatic epithelial cell line were subjected to qRT-PCR assay to evaluate the expression levels of LINC00460. CCK-8 assays were used to detect the proliferation of HCC cells. Transwell assay was used to measure the migration and invasion abilities of HCC cells. RNA pull-down and luciferase assays were performed to verify the direct interaction between LINC00460 and miR-342-3p. A xenograft model of HCC was established to validate the in vivo function of LINC00460 in HCC progression.
We firstly detected LINC00460 expression was significantly upregulated in both HCC tumor tissues and cell lines. The upregulation of LINC00460 was positively associated with HCC progression. Functionally, LINC00460 facilitated HCC cell proliferation, migration, and invasion capacities, which due to that LINC00460 could physically bind to and repress miR-342-3p to elevate the expression of AGR2.
Our data firstly reveal the clinical relevance, biological function, and regulatory mechanism of LINC00460 in HCC development. LINC00460 promotes HCC progression by elevating AGR2 expression via sponging miR-342-3p, providing a promising therapeutic target for HCC treatment.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因。LINC00460是一种新型长链非编码RNA（lncRNA），最近被确认为多种癌症中的致癌基因。然而，LINC00460在HCC中的生物学功能和潜在机制在很大程度上尚不清楚。
对50对HCC患者的肿瘤组织和癌旁正常组织，以及6种HCC细胞系和1种正常人肝上皮细胞系进行qRT-PCR检测，以评估LINC00460的表达水平。采用CCK-8法检测HCC细胞的增殖情况。采用Transwell法检测HCC细胞的迁移和侵袭能力。进行RNA下拉和荧光素酶检测，以验证LINC00460与miR-342-3p之间的直接相互作用。建立HCC异种移植模型，以验证LINC00460在HCC进展中的体内功能。
我们首先检测到LINC00460在HCC肿瘤组织和细胞系中均显著上调。LINC00460的上调与HCC进展呈正相关。在功能上，LINC00460促进了HCC细胞的增殖、迁移和侵袭能力，这是因为LINC00460可以与miR-342-3p物理结合并抑制其表达，从而提高AGR2的表达。
我们的数据首次揭示了LINC00460在HCC发生发展中的临床相关性、生物学功能和调控机制。LINC00460通过海绵吸附miR-342-3p提高AGR2表达促进HCC进展，为HCC治疗提供了一个有前景的治疗靶点。
