Long noncoding RNA LINC01124 activates hepatocellular carcinoma cell proliferation, migration, and invasion by absorbing microRNA-1247-5p and overexpressing FOXO3

Abstract

Long intergenic non-protein coding RNA 1124 (LINC01124) has been identified as an important regulator of non-small-cell lung cancer. However, the expression and detailed role of LINC01124 in hepatocellular carcinoma (HCC) remain unestablished to date. Therefore, this study aimed to elucidate the role of LINC01124 in the aggressiveness of HCC cells and identify the underlying regulatory mechanism. Quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression of LINC01124 in HCC. Cell Counting Kit-8 assay, Transwell cell migration and invasion assays, and a xenograft tumor model were used to investigate the function of LINC01124 in HCC cells, and bioinformatics analysis, RNA immunoprecipitation, luciferase reporter assay, and rescue experiments were used to elucidate the underlying mechanisms. Herein, LINC01124 overexpression was confirmed in HCC tissues as well as cell lines. Further, the downregulation of LINC01124 decreased HCC cell proliferation, migration, and invasion in vitro, whereas the upregulation of LINC01124 triggered the opposite results. Additionally, LINC01124 ablation impaired tumor growth in vivo. Mechanistic analyses revealed that LINC01124 functions as a competing endogenous RNA to sponge microRNA-1247-5p (miR-1247-5p) in HCC cells. Moreover, forkhead box O3 (FOXO3) was identified as a direct target of miR-1247-5p. FOXO3 was positively regulated by LINC01124 in HCC cells through the sequestration of miR-1247-5p. Finally, rescue assays revealed that the inhibition of miR-1247-5p or overexpression of FOXO3 reversed the effects of LINC01124 silencing on the HCC cell malignant phenotype. In summary, LINC01124 plays a tumor-promoting role in HCC by regulating the miR-1247-5p-FOXO3 axis. The LINC01124-miR-1247-5p-FOXO3 pathway may provide a foundation for the identification of alternative therapies for HCC.

A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility

“…Another study revealed that LINC01977 accelerated LIHC progression by inhibiting Notch2 ubiquitination and depletion, suggesting that LINC01977 could be a potential biomarker and therapeutic target for LIHC patients 63 . Similarly, Sun et al indicated that LINC01124 played a tumor-promoting role in LIHC through regulating the miR-1247-5p-FOXO3 axis 65 . Interestingly, the crucial role of RCD-related abnormally expressed lncRNAs in monitoring and promoting the development and progression of LIHC is drawing growing interest.…”

“…Emerging research highlights critical roles of lncRNAs to the LIHC development and progression 63 – 65 . Recently, Chi et al found that the lncRNA PTOV1-AS1 is up-regulation in LIHC and associated with patients’ prognosis and sorafenib resistance 64 .…”

PTBP1-mediated biogenesis of circATIC promotes progression and cisplatin resistance of bladder cancer

“…Expression analysis, TRAP assay and dual luciferase reporter assay were used to verify that miR-1247-5p was the target gene of circATIC. MiR-1247-5p plays a tumor suppressor role in multiple cancers 27 , 29 , 66 . Our studies validated the significant decrease of miR-1247-5p in 52 BLca tissues compared to normal tissues, leading to enhanced proliferation, migration and invasion of BLca cells via targeting Regulator of chromosome condensation 2 (RCC2).…”