Department of Infectious Disease, Central Hospital of Suizhou City, Suizhou Hospital Affiliated to Hubei Medical College, Suizhou, Hubei 441300, China.
Gastroenterology Ward, Yantai Yuhuangding Hospital, No.20 of Yudong Road, Zhifu District, Yantai 264000, Shandong, China.
Clin Res Hepatol Gastroenterol. 2021 Mar;45(2):101648. doi: 10.1016/j.clinre.2021.101648. Epub 2021 Feb 12.
Long non-coding RNA 01559 (LINC01559) has been found to be associated with the tumorigenesis of malignant tumors. However, the expression pattern and the potential molecular mechanism of LINC01559 in hepatocellular carcinoma (HCC) progression remain unclear.
Expression profile and clinical data of patients with HCC were retrieved from The Cancer Genome Atlas database. The quantitative real-time PCR (qRT-PCR) and western blot assays were used to detect the mRNA and protein levels of indicated molecules. Loss-of-function of LINC01559 and microRNA-511 (miR-511) assays were implemented to validate their roles in regulating proliferation, invasion and migration of HCC HepG2 and Huh7 cells. Bioinformatics and luciferase reporter assays were used to determine the possible interactions between LINC01559, miR-511 and solute carrier family 38 member 1 (SLC38A1).
LINC01559 was highly expressed, and related to poor prognosis in HCC patients. LINC01559-knockdown restrained the proliferation and growth of HepG2 and Huh7 cells. Furthermore, LINC01559 can function as a sponge for miR-511, which was downregulated in HCC patients. Downregulation of miR-511 significantly increased the cell viability, invasive and migratory capacities, and could abolish the suppressive effect of LINC01559-knockdown on these HCC cells. Moreover, SLC38A1 was a target of miR-511 and upregulated in HCC. Knockdown of LINC01559 significantly reduced while miR-511 inhibitor notably elevated the mRNA and protein levels of SLC38A1, which were abrogated by downregulation of LINC01559 and miR-511 simultaneously.
LINC01559 functioned as a competitive endogenous RNA mediating the malignant phenotypes of HCC cells via sponging miR-511, and may be a considerable therapeutic bio-target in HCC.
长链非编码 RNA 01559（LINC01559）已被发现与恶性肿瘤的发生有关。然而，LINC01559 在肝细胞癌（HCC）进展中的表达模式和潜在分子机制尚不清楚。
从癌症基因组图谱数据库中检索了 HCC 患者的表达谱和临床数据。采用实时定量 PCR（qRT-PCR）和 Western blot 检测法检测了指示分子的 mRNA 和蛋白水平。通过 LINC01559 缺失功能和 microRNA-511（miR-511）检测来验证其在调节 HCC HepG2 和 Huh7 细胞增殖、侵袭和迁移中的作用。通过生物信息学和荧光素酶报告基因检测来确定 LINC01559、miR-511 和溶质载体家族 38 成员 1（SLC38A1）之间可能的相互作用。
LINC01559 高表达，与 HCC 患者的不良预后相关。LINC01559 敲低抑制了 HepG2 和 Huh7 细胞的增殖和生长。此外，LINC01559 可以作为 miR-511 的海绵体，miR-511 在 HCC 患者中下调。miR-511 的下调显著增加了细胞活力、侵袭和迁移能力，并能消除 LINC01559 敲低对这些 HCC 细胞的抑制作用。此外，SLC38A1 是 miR-511 的靶基因，在 HCC 中上调。LINC01559 的敲低显著降低，而 miR-511 抑制剂显著升高 SLC38A1 的 mRNA 和蛋白水平，同时下调 LINC01559 和 miR-511 则消除了这一作用。
LINC01559 通过海绵吸附 miR-511 发挥竞争性内源性 RNA 的作用，调节 HCC 细胞的恶性表型，可能是 HCC 有前途的治疗生物靶点。
