LINC00221 silencing prevents the progression of hepatocellular carcinoma through let-7a-5p-targeted inhibition of MMP11

Abstract

Background Microarray profiles of hepatocellular carcinoma (HCC) identified that long intergenic noncoding RNA 00221 (LINC00221) was upregulated. Herein, we aimed to identify the functional significance and underlying mechanisms of LINC00221 in HCC. Methods and results Human HCC samples had increased expression of LINC00221. Effects of LINC00221 on HCC cellular functions were analyzed using gain- and loss-function approaches. LINC00221 knockdown repressed HCC cell growth, migration, and invasion and enhanced their apoptosis. This anti-tumor effect was validated in vivo. Online prediction showed the potential binding relationship between LINC00221 and let-7a-5p, as well as that between let-7a-5p and matrix metalloproteinase 11 (MMP11). The results of luciferase, RNA immunoprecipitation, and RNA pull-down assays identified that LINC00221 interacted with let-7a-5p to increase expression of MMP11. Furthermore, we demonstrated that LINC00221 silencing increased let-7a-5p and inhibited MMP11 expression, thereby delaying the progression of HCC in vitro. Conclusions Silencing of LINC00221 could prevent HCC progression via upregulating let-7a-5p and downregulating MMP11. As such, LINC00221 inhibition presents a promising antitumor strategy for the treatment of HCC.

Bioinformatics Analysis Combined With Experiments Predicts PUDP as a Potential Prognostic Biomarker for Hepatocellular Carcinoma Through Its Interaction With Tumor Microenvironment

“…19 miRNAs were finally obtained. In HCC, the majority of miRNAs have been found to function as tumor suppressor, for example, upregulated let-7a-5p could prevent HCC progression ( 55 ). In the end, the most potential upstream tumor suppressor miRNA for PUDP was identified as let-7c-5p after correlation analysis, expression analysis, and survival analysis.…”

Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study

“…Our results proposed combinations of let-7a-5p and miR-1246, let-7f-5p and miR-4532, miR-320c and let-7a-5p, miR-122-5p and let-7a-5p and the selected panel, namely, miR-320b/c and let-7a-5p, that showed the highest AUC of 0.9822. Of these three miRNAs, only let-7a-5p is supported by multiple studies indicating that let-7a-5p can modulate cell growth, migration and invasion, cell proliferation and apoptosis, and importantly, that it is associated with hepatis B and viral carcinogenesis, as indicated in Figure 4 [60][61][62][63][64]. In a Chinese cohort where 74.8% of patients were HBV positive, three serum-exosome-derived miRNAs (miR-122-5p, let-7d-5p and miR-425-5p) with an AUC of 0.905 were identified as promising biomarkers for identifying HCC patients [225].…”

Development and Validation of Genome Instability-Associated lncRNAs to Predict Prognosis and Immunotherapy of Patients With Hepatocellular Carcinoma

“…Human HCC samples had increased the expression of LINC00221. LINC00221 knockdown repressed HCC cell growth, migration, and invasion and enhanced their apoptosis (Yang et al, 2021). ZFPM2-AS1 was observed to be distinctly upregulated in HCC tissues and associated with shorter overall survival.…”