Oncogene, 2020-06, Vol.39 (23), p.4538-4550
2020
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- Autor(en) / Beteiligte
- Titel
- The β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 axis promotes hepatocellular carcinoma metastasis
- Ist Teil von
- Oncogene, 2020-06, Vol.39 (23), p.4538-4550
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Cancer Genome Atlas (TCGA) and Sun Yat-sen University Cancer Center (SYSUCC) dataset. MiR-1258 expression negatively correlated with recurrence-free survival and overall survival of HCC patients. MiR-1258 overexpression inhibited migration and invasion of HCC cells both in vitro and in vivo, whereas miR-1258 downregulation promoted cell metastasis. Luciferase assays verified direct binding of miR-1258 to Smad2 and Smad3, thereby attenuating TGF-β/Smad signaling. We further established that lncRNA LINC01278 was a negative regulator of miR-1258. In vivo and in vitro assays demonstrated that LINC01278-mediated HCC metastasis was dependent on miR-1258 expression. Furthermore, miR-1258 downregulation in turn increased LINC01278 expression. We also observed that TCF-4 could bind to the LINC01278 promoter site. In addition, LINC01278 downregulation decreased migration and invasion of HCC cells induced by β-catenin and TGF-β1 both in vitro and in vivo. We uncovered a novel mechanism for β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 feedback loop activation in HCC metastasis, and the study indicated that LINC01278 could serve as a therapeutic target for HCC metastasis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/s41388-020-1307-3Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7269911
- Format
- –
- Schlagworte
- Animals, beta Catenin - metabolism, Carcinoma, Hepatocellular - pathology, Cell Line, Tumor, Cell Movement - genetics, Genomes, Hepatocellular carcinoma, Humans, Liver cancer, Liver Neoplasms - pathology, Lymphoid Enhancer-Binding Factor 1 - metabolism, Metastases, Metastasis, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs - genetics, Neoplasm Metastasis - pathology, Neoplasm Transplantation, Non-coding RNA, RNA, Long Noncoding - genetics, Smad protein, Smad2 protein, Smad2 Protein - metabolism, Smad3 protein, Smad3 Protein - metabolism, Therapeutic applications, Therapeutic targets, Transcription Factor 4 - genetics, Transcription Factor 4 - metabolism, Transforming Growth Factor beta - metabolism, Transforming growth factor-b1, Transplantation, Heterologous, Wnt Signaling Pathway - physiology, Wnt1 Protein - metabolism, β-Catenin