Abstract
BackgroundMicroarray 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 resultsHuman 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.ConclusionsSilencing 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.
Highlights
Microarray profiles of hepatocellular carcinoma (HCC) identified that long intergenic noncoding RNA 00221 (LINC00221) was upregulated
LncRNAs are a group of non-protein-coding transcripts with a length of 200 or more nucleotides; dysregulation of long non-coding RNAs (lncRNAs) possibly contributes to development and progression of
Higher LINC00221 expression was observed in Huh7 and MHCC97-H cell lines than in HL-7702, so these two cell lines were selected for subsequent cell experiments (Fig. 1e)
Summary
Microarray profiles of hepatocellular carcinoma (HCC) identified that long intergenic noncoding RNA 00221 (LINC00221) was upregulated. Long intergenic noncoding RNA 00,221 (LINC00221), known as NCRNA00221 [9], is an lncRNA recognized to be a potential prognostic biomarker for HCC [10]. LncRNAs have been widely identified to function as competitive endogenous RNAs (ceRNAs) or sponges of microRNAs (miRNAs), mediating effects on the post-transcription regulation of mRNAs [11]. A previous study has suggested that the lncRNA Ras suppressor protein 1 pseudogene 2 (RSU1P2) mediates gene expression in cervical cancer by functioning as a ceRNA of let-7a [12]. We hypothesized that LINC00221 might have a crucial modulatory effect on the growth of HCC cells through the let-7a-5p/ MMP11 axis
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