Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
J Cell Biochem. 2019 Oct;120(10):16393-16407. doi: 10.1002/jcb.28549. Epub 2019 Jul 3.
Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. It has been shown that long noncoding RNA (lncRNA) might play a role in HCC. The aim of the present study was to identify the role of long intergenic noncoding RNA 01551 (LINC01551) in the HCC development and explore the underlying mechanism of LINC01551/miR-122-5p/ADAM10 axis. The differentially expressed lncRNAs associated with HCC were screened out by a microarray analysis. The expression of LINC01551, miR-122-5p, and ADAM10 was determined in HCC tissues and cells. The potential miRNA (miR-122-5p) regulated by LINC01551 was explored, and the target relationship between miR-122-5p and ADAM10 was confirmed. To evaluate the effect of LINC01551 and miR-122-5p on proliferation, migration, invasion, and apoptosis of HCC, different plasmids were delivered into MHCC97-H cells. High expression of LINC01551 and ADAM10 yet low-expression of miR-122-5p were revealed in HCC tissues and cells. Overexpression of miR-122-5p could downregulate ADAM10. Biological prediction websites and fluorescence in situ hybridization assay verified that LINC01551 was mainly expressed in the cytoplasm. Silencing LINC01551 reduced HCC cell viability, proliferation, migration, invasion, and cell cycle entry yet induce cell apoptosis. Upregulation of LINC01551 increased its ability of competitively binding to miR-122-5p, thus reducing miR-122-5p and upregulating ADAM10 expression, as well as promoting the proliferative, migrative, and invasive ability. Taken together the results, it is highly possible that LINC01551 functions as an competing endogenous RNA (ceRNA) to regulate the miRNA target ADAM10 by sponging miR-122-5p and therefore promotes the development of HCC, highlighting a promising competitive new target for the HCC treatment.
肝细胞癌（HCC）是一种死亡率很高的全球性严重疾病。已经表明，长非编码 RNA（lncRNA）可能在 HCC 中发挥作用。本研究的目的是确定长基因间非编码 RNA 01551（LINC01551）在 HCC 发展中的作用，并探讨 LINC01551/miR-122-5p/ADAM10 轴的潜在机制。通过微阵列分析筛选出与 HCC 相关的差异表达 lncRNA。测定 HCC 组织和细胞中 LINC01551、miR-122-5p 和 ADAM10 的表达。探讨了受 LINC01551 调控的潜在 miRNA（miR-122-5p），并证实了 miR-122-5p 和 ADAM10 之间的靶关系。为了评估 LINC01551 和 miR-122-5p 对 HCC 增殖、迁移、侵袭和凋亡的影响，将不同的质粒转染到 MHCC97-H 细胞中。结果显示，LINC01551 和 ADAM10 在 HCC 组织和细胞中高表达，而 miR-122-5p 低表达。miR-122-5p 的过表达可下调 ADAM10。生物预测网站和荧光原位杂交实验证实 LINC01551 主要在细胞质中表达。沉默 LINC01551 降低了 HCC 细胞的活力、增殖、迁移、侵袭和细胞周期进入，同时诱导细胞凋亡。上调 LINC01551 增加了其与 miR-122-5p 竞争结合的能力，从而降低 miR-122-5p 并上调 ADAM10 表达，促进增殖、迁移和侵袭能力。总之，LINC01551 可能作为竞争性内源性 RNA（ceRNA）通过海绵吸附 miR-122-5p 调节 miRNA 靶 ADAM10，从而促进 HCC 的发展，为 HCC 的治疗提供了有前景的新竞争靶点。
