Abstract
BackgroundAccumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown.MethodsThe expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo.ResultsWe found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2.ConclusionTUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.
Highlights
Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis
TUG1 was validated to act as a molecular sponge of miR-216b-5p
The results showed that the luciferase activity of TUG1 wild type (TUG1-WT) in Hep3B and Huh7 cells was decreased by the miR-216b-5p mimic, but the TUG1MUT activity was not significantly changed (Fig. 2b, c)
Summary
Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. The overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. Non-coding RNAs (ncRNAs), containing widely studied microRNAs (miRNAs) and latterly identified long non-coding RNAs (lncRNAs), have been served as oncogenes or tumor suppressor genes for various tumors, becoming new potential therapeutic targets [5, 6]. LncRNAs are known as RNA molecules longer than 200 nucleotides without coding capacity [7]. It’s worth mentioning that lncRNAs could play a part of competitive endogenous RNAs (ceRNAs) to interplay with miRNAs and regulate the miRNA targeted gene expression [10]
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