Downregulation of miR-610 promotes proliferation and tumorigenicity and activates Wnt/β-catenin signaling in human hepatocellular carcinoma

Zhang, Xiancheng; Liu, Fo-Qiu; Yan, Rongguo; Yi, Huimin; Zhang, Tong; Wang, Guoying; Yang, Li; Jiang, Nan

doi:10.1186/1476-4598-13-261

Cited by 40 publications

(29 citation statements)

References 51 publications

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“…We and others have provided data to support the involvement of small ncRNAs, such as microRNAs, in the modulation of liver cell proliferation and apoptosis 10–13. Despite several studies linking ncRNA and the Wnt pathway, most of them focused on the modulation of Wnt signalling proteins by microRNAs, little is known about the effect of this pathway on ncRNA 14–17. Increasing evidence points to an important regulatory role of long ncRNAs in cellular processes and disease phenotypes.…”

Section: Introductionmentioning

confidence: 97%

Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers

Carotenuto

Fassan

Pandolfo

et al. 2016

Gut

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ObjectiveTranscribed-ultraconserved regions (T-UCR) are long non-coding RNAs which are conserved across species and are involved in carcinogenesis. We studied T-UCRs downstream of the Wnt/β-catenin pathway in liver cancer.DesignHypomorphic Apc mice (Apcfl/fl) and thiocetamide (TAA)-treated rats developed Wnt/β-catenin dependent hepatocarcinoma (HCC) and cholangiocarcinoma (CCA), respectively. T-UCR expression was assessed by microarray, real-time PCR and in situ hybridisation.ResultsOverexpression of the T-UCR uc.158− could differentiate Wnt/β-catenin dependent HCC from normal liver and from β-catenin negative diethylnitrosamine (DEN)-induced HCC. uc.158− was overexpressed in human HepG2 versus Huh7 cells in line with activation of the Wnt pathway. In vitro modulation of β-catenin altered uc.158− expression in human malignant hepatocytes. uc.158− expression was increased in CTNNB1-mutated human HCCs compared with non-mutated human HCCs, and in human HCC with nuclear localisation of β-catenin. uc.158− was increased in TAA rat CCA and reduced after treatment with Wnt/β-catenin inhibitors. uc.158− expression was negative in human normal liver and biliary epithelia, while it was increased in human CCA in two different cohorts. Locked nucleic acid-mediated inhibition of uc.158− reduced anchorage cell growth, 3D-spheroid formation and spheroid-based cell migration, and increased apoptosis in HepG2 and SW1 cells. miR-193b was predicted to have binding sites within the uc.158− sequence. Modulation of uc.158− changed miR-193b expression in human malignant hepatocytes. Co-transfection of uc.158− inhibitor and anti-miR-193b rescued the effect of uc.158− inhibition on cell viability.ConclusionsWe showed that uc.158− is activated by the Wnt pathway in liver cancers and drives their growth. Thus, it may represent a promising target for the development of novel therapeutics.

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Section: Introductionmentioning

confidence: 97%

Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers

Carotenuto

Fassan

Pandolfo

et al. 2016

Gut

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“…6). LRP6 has been shown to function as an oncogene by promoting cell growth, invasion and migration, and is expected to be a target for cancer therapy (40)(41)(42)(43)(44)(45). Notably, there is evidence that ERK1/2 in the RAS/MAPK pathway could facilitate WNT/β-catenin signaling via LRP6 phosphorylation on serine-1490 (S1490) and threonine-1572 (T1572) at both mature (transmenbrane LRP6) and immature state during its Golgi network-based maturation process (46,47).…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

Hata

Mokutani

Takahashi

et al. 2016

International Journal of Oncology

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Abstract.Recent studies have shown that microRNAs (miRNAs) are involved in the progression of colorectal cancer (CRC). The aim of this study is to identify a novel miRNA that especially relates to liver metastasis and to explore the underlying mechanism. Differentially expressed miRNAs were analyzed using microarray, in primary CRC tumors without metastasis (n=16), those with liver metastasis (n=12), and liver metastatic lesions (n=8). We found that miR-487b level decreased in liver metastatic lesions, and qRT-PCR confirmed the results in the validating cohort (n=134). Survival analysis indicated that high expression of miR-487b was associated with better prognosis. In vitro studies were also performed to investigate the functional significance of miR-487b in human CRC cell lines. miR-487b showed an inhibitory effect on cell proliferation and invasion of CRC cells. miR-487b downregulated KRAS and inhibited its downstream signal pathways, and the luciferase reporter assay revealed that miR-487b directly targeted LRP6, a receptor for WNT/β-catenin signaling. These findings showed that decrease in miR-487b was related with liver metastasis. Our data suggest a possibility that miR-487b may suppress metastasis of CRC progression through inhibition of KRAS.

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“…TBL1X is a potential target of miR-138-5p, as predicted by the IPA's microRNA Target Filter tool. TBL1X functions as an oncogene in the proliferation and tumorigenesis of hepatocellular carcinoma (HCC) cells through activating WNT/β-catenin signaling [47]. The bioinformatics approaches in our study revealed that the miRNA signature identified gene targets involved in the WNT/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 93%

Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus

Ding

Guo

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The placenta has been suggested to play a crucial role in the pathology of gestational diabetes mellitus (GDM). Placenta-specific microRNAs (miRNAs) and the corresponding targeting genes involved in the pathology of GDM still remain to be elucidated. We aimed to identify the dysregulated miRNAs and the corresponding mRNA targets through an integrated miRNA and mRNA transcriptomic profiles analysis and investigate the role of differentially expressed miR-138-5p/TBL1X in GDM. Methods: RNA sequencing (RNA-seq) was performed in 16 placentas from GDM and control group. Differentially expressed mRNAs and miRNAs in GDM were validated by quantitative PCR (qPCR). The wound healing assay and transwell migration assay were used to analyze cell migration ability. The cell proliferation was determined by CCK8 assay. Luciferase assay was used to confirm the direct binding of the targeted TBL1X with miR-138-5p. Results: Totally, 281 mRNAs and 32 miRNAs were found to be differentially expressed in the GDM placentas. The biological relationships of the miRNA/mRNA pairs were related to cellular development and function and organ morphology. Among the aberrantly expressed molecules, we selected miR-138-5p from the bioinformatics analysis and found that miR-138-5p significantly inhibited the migration and proliferation of trophoblasts (HTR-8/SVneo) by targeting the 3’-UTR of TBL1X. Furthermore, the aberrant expression of miR-138-5p and TBL1X was significantly correlated with the weight of the placenta. Conclusion: We present the first integrative analysis of miRNA and mRNA expression profiles in GDM placenta and uncover a more detailed role for miR-138-5p, as well as its target TBL1X in the pathology of GDM.

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Downregulation of miR-610 promotes proliferation and tumorigenicity and activates Wnt/β-catenin signaling in human hepatocellular carcinoma

Cited by 40 publications

References 51 publications

Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers

Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus

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