Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma
Ling Zhang,Fu Yang,Ji-hang Yuan,Sheng-xian Yuan,Weiping Zhou,Xi-song Huo,Dan Xu,Hai-shan Bi,Fang Wang,Shuhan Sun +9 more
TLDR
It is shown that H19 was underexpressed in intratumoral HCC tissues (T), as compared with peritumoral tissues (L), and low T/L ratio of H19 predicted poor prognosis, which could suggest the development of combination therapies that target H19 and the miR-200 family.Abstract:
Although numerous long non-coding RNAs (lncRNAs) have been identified in mammals, many of their biological roles remain to be characterized. Early reports suggest that H19 contributes to carcinogenesis, including hepatocellular carcinoma (HCC). Examination of the Oncomine resource showed that most HCC cases express H19 at a level that is comparable with the liver, with a tendency toward lower expression. This is consistent with our previous microarray data and indicates a more complicated role of H19 in HCC that needs to be characterized. In this study, the expression level of H19 was assessed in different regions of HCC patients' liver samples. Loss- and gain-of-function studies on this lncRNA in the HCC cell lines, SMMC7721 and HCCLM3, were used to characterize its effects on gene expression and to assess its effect on HCC metastasis both in vitro and in vivo. In this study, we show that H19 was underexpressed in intratumoral HCC tissues (T), as compared with peritumoral tissues (L). Additionally, low T/L ratio of H19 predicted poor prognosis. H19 suppressed HCC progression metastasis and the expression of markers of epithelial-to-mesenchymal transition. Furthermore, H19 associated with the protein complex hnRNP U/PCAF/RNAPol II, activating miR-200 family by increasing histone acetylation. The results demonstrate that H19 can alter the miR-200 pathway, thus contributing to mesenchymal-to-epithelial transition and to the suppression of tumor metastasis. These data provide an explanation for the hitherto puzzling literature on the relationship between H19 and cancer, and could suggest the development of combination therapies that target H19 and the miR-200 family.read more
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Journal ArticleDOI
Molecular pattern of lncRNAs in hepatocellular carcinoma.
TL;DR: Recent discoveries regarding HCC-associated lncRNA functions are comprehensively reviewed and classified and described according to their mechanism models.
Journal ArticleDOI
H19 Promotes HCC Bone Metastasis Through Reducing Osteoprotegerin Expression in a Protein Phosphatase 1 Catalytic Subunit Alpha/p38 Mitogen-Activated Protein Kinase-Dependent Manner and Sponging microRNA 200b-3p.
Zhao Huang,Liang Chu,Junnan Liang,Xiaolong Tan,Yu Wang,Jingyuan Wen,Jin Chen,Yu Wu,Sha Liu,Jingyu Liao,Rui Hou,Zeyang Ding,Zhanguo Zhang,Huifang Liang,Shasha Song,Caihong Yang,Jinming Zhang,Tao Guo,Xiaoping Chen,Bixiang Zhang +19 more
TL;DR: H19 plays a critical role in HCC bone metastasis by reducing OPG expression, which is mediated by the PPP1CA-induced inactivation of the p38MAPK pathway, and H19 also functions as a sponge for miR-200b-3p.
Journal ArticleDOI
Long noncoding RNA H19 is up-regulated in esophageal squamous cell carcinoma and promotes cell proliferation and metastasis.
TL;DR: Findings indicate that H19 acts as an oncogene and promotes ESCC cell proliferation and metastasis, which may infer H19 as a marker of poor prognosis and, thus, a potential therapeutic target for treating ESCC patients.
Journal ArticleDOI
A novel long non-coding RNA FGF14-AS2 is correlated with progression and prognosis in breast cancer.
TL;DR: It is demonstrated that FGF14 antisense RNA 2 (FGF14-AS2), a novel long non-coding RNA, was significantly down-regulated in breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort.
Journal ArticleDOI
Long noncoding RNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429 in melanoma.
Xiangjun Chen,Sha Liu,Xiao-chun Zhao,Xiao Ma,Guozhen Gao,Li Yu,Dexiong Yan,Hao Dong,Sun Weijing +8 more
TL;DR: It is demonstrated that melanoma-upregulated lncRNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429, and imply that ILF2-AS2 may be a potential prognostic biomarker and therapeutic target for melanoma.
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