The online version of this article (https://doi.org/10.1186/s13046-018-0853-9) contains supplementary material, which is available to authorized users.
Shaoying Yan and Zhenrong Tang contributed equally to this work.
Emerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested that MIR31HG could act as either oncogene or tumor suppressor. But the functional involvement of MIR31HG has not been studied in hepatocellular carcinoma (HCC).
In this study, MTS assays, colony formation assay, Wound-healing assay, Transwell assy, and tumor xenografts experiments were used to identify biological effects of MIR31HG on HCC cells HCC proliferation and metastasis in vitro and in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to show the interactions of MIR31HG and miR-575. The bioinformatics methods were completed to find the target genes of miR-575. And Dual-luciferase reporter assay and Western blot analysis were further used to confirm the target gene of miR-575.
We found that overexpression of MIR31HG obviously suppressed HCC proliferation and metastasis in vitro and in vivo, whereas knockdown of MIR31HG had the opposite effects. Besides, overexpression of MIR31HG significantly decreased the expression of microRNA-575 (miR-575), which plays an oncogenic role in HCC. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay revealed that MIR31HG exerted tumor-suppressive functions by binding directly to miR-575, and there was a reciprocal inhibition between MIR31HG and miR-575 in the same RNA-induced silencing complex (RISC). Furthermore, overexpression of MIR31HG enhanced the expression of suppression of tumorigenicity 7 like (ST7L), which was identified as a downstream target gene of miR-575. Thus, MIR31HG positively regulated ST7L expression through sponging miR-575, and acted as tumor suppressor in HCC.
Overall, our study illuminates the role of MIR31HG as a miRNA sponge in HCC, and sheds new light on lncRNA-directed diagnostics and therapeutics in HCC.
Additional file 1: Table S1. Quantitative real-time PCR primer sequences. (DOC 42 kb)13046_2018_853_MOESM1_ESM.doc
Additional file 2: Figure S1. a The efficiencies of MIR31HG overexpression and silencing were confirmed with qRT-PCR. b The efficiencies of miR-575 overexpression and silencing were confirmed with qRT-PCR. (TIF 260 kb)13046_2018_853_MOESM2_ESM.tif
Additional file 3 Figure S2. a The expressions of 10 potential miRNAs in pcDNA3.1 groups and pcDNA3.1-MIR31HG were detected with qRT-PCR analysis. b The expressions of 8 potential genes in pcDNA3.1 groups and pcDNA3.1-MIR31HG were detected with qRT-PCR analysis. (TIF 332 kb)13046_2018_853_MOESM3_ESM.tif
Additional file 4 Figure S3. a The expressions of MIR31HG in pcDNA3.1 + pre-NC group, pcDNA3.1 + anti-NC group, sh-NC + anti-NC group and sh-NC + pre-NC group were detected with qRT-PCR analysis. b The expressions of miR-575 in pcDNA3.1 + pre-NC group, pcDNA3.1 + anti-NC group, sh-NC + anti-NC group and sh-NC + pre-NC group were detected with qRT-PCR analysis. (TIF 310 kb)13046_2018_853_MOESM4_ESM.tif
Yao Y, Suo AL, Li ZF, Liu LY, Tian T, Ni L, et al. MicroRNA profiling of human gastric cancer. Mol Med Rep. 2009;2:963–70. PubMed
Katoh M. Molecular cloning and characterization of ST7R (ST7-like, ST7L) on human chromosome 1p13, a novel gene homologous to tumor suppressor gene ST7 on human chromosome 7q31. Int J Oncol. 2002;20:1247–53. PubMed
- Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression
- BioMed Central
Journal of Experimental & Clinical Cancer Research
Elektronische ISSN: 1756-9966
Neu im Fachgebiet Onkologie
Mail Icon II