Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Putian University, Putian, Fujian, China.
Department of General Medicine, Affiliated Hospital of Putian University, Putian, Fujian, China.
Bioengineered. 2022 Apr;13(4):11228-11239. doi: 10.1080/21655979.2022.2063648.
As a malignant tumor, HCC (hepatocellular carcinoma) is featured by a high recurrence rate with a poor prognosis. Increasing evidence supports an important role of lincRNAs in HCC. Here, the purpose of the study was to explore the function of LINC00978 (long non-coding RNA00978) in HCC and the underlying mechanisms. LINC00978 expression and its association with the progression of HCC were analyzed using HCC TCGA datasets. LINC00978 expression in tissues was measured using real-time PCR. Then, we knocked down LINC00978 in HCC cells to explore its effect on cellular invasion, proliferation, and migration. Finally, we investigated the potential molecular mechanism of LINC00978 by dual Luciferase reporter assay, FISH (fluorescence in situ hybridization) and RIP (RNA immunoprecipitation). LINC00978 expression was remarkably increased in HCC. A high level of LINC00978 was associated with poor prognosis of HCC. Additionally, LINC00978 silencing could repress the growth and metastasis of HCC cells. Mechanistically, it was revealed that LINC00978 could sponge microRNA-125b-5p and identified SOX12 (SRY-Box Transcription Factor 12) as a direct target gene of microRNA-125b-5p. More importantly, the suppressed effect of LINC00978 silencing on the metastasis and growth of HCC cells could be rescued by miR-125b-5p inhibition and overexpressed SOX12. LINC00978/microRNA-125b-5p/SOX12 axis promoted liver cancer migration, invasion, and proliferation, which could be used as a possible therapeutic target for the treatment of hepatocellular carcinoma.
作为一种恶性肿瘤，肝癌（HCC）的特点是复发率高，预后差。越来越多的证据支持 lincRNAs 在 HCC 中的重要作用。本研究旨在探讨 LINC00978（长链非编码 RNA00978）在 HCC 中的功能及其潜在机制。使用 HCC TCGA 数据集分析 HCC 中 LINC00978 的表达及其与 HCC 进展的关系。采用实时 PCR 检测组织中 LINC00978 的表达。然后，我们在 HCC 细胞中敲低 LINC00978，以探讨其对细胞侵袭、增殖和迁移的影响。最后，通过双荧光素酶报告基因检测、FISH（荧光原位杂交）和 RIP（RNA 免疫沉淀）实验研究 LINC00978 的潜在分子机制。结果表明，LINC00978 在 HCC 中表达显著上调，高水平的 LINC00978 与 HCC 的不良预后相关。此外，LINC00978 沉默可抑制 HCC 细胞的生长和转移。机制研究表明，LINC00978 可以海绵吸附 microRNA-125b-5p，并确定 SOX12（SRY-Box 转录因子 12）为 microRNA-125b-5p 的直接靶基因。更重要的是，LINC00978 沉默对 HCC 细胞转移和生长的抑制作用可以通过抑制 miR-125b-5p 和过表达 SOX12 来挽救。LINC00978/microRNA-125b-5p/SOX12 轴促进肝癌迁移、侵袭和增殖，可作为治疗肝细胞癌的潜在治疗靶点。
