Dataset Information

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1.

ABSTRACT:

Purpose

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently, microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanisms of miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration, invasion, and epithelial-mesenchymal transition (EMT).

Materials and methods

We investigated the key roles and possible regulatory mechanism of miR-370 in regulating HCC metastasis with functional assays, such as transwell assay. Quantitative real-time PCR (qRT-PCR) was used to detect miR-370 and guanylylcyclase domain containing 1 (GUCD1) expression in HCC tissues and cells. Subsequently, we performed transwell assays to determine the functions of miR-370 in HCC cell invasion and migration. Western blot was used to determine protein expressions of relevant genes. Luciferase reporter assays were conducted to confirm the target gene of miR-370.

Results

qRT-PCR analysis demonstrated that miR-370 was dramatically downregulated in HCC. Moreover, downregulated miR-370 was found to be associated with poor survival and adverse clinicopathologic characteristics of HCC patients. Transwell assays revealed that miR-370 overexpression dramatically suppressed HCC invasion and migration. Meanwhile, miR-370 restoration prominently inhibited EMT progression in HCC cells. Luciferase reporter assays confirmed GUCD1 as a downstream target gene of miR-370. GUCD1 expression in HCC tissues was prominently increased and inversely correlated with miR-370 expression. Furthermore, GUCD1 was verified as mediating the suppressive influence of miR-370 on cell metastasis and EMT in HCC.

Conclusion

Taken together, our study confirmed that miR-370 suppressed HCC cell metastasis and EMT via regulating GUCD1. Accordingly, the miR-370/GUCD1 axis may potentially acts as attractive therapeutic targets and novel biomarkers for HCC treatment.

SUBMITTER: He Y

PROVIDER: S-EPMC6391526 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1.

He Yongkang Y He Xiaofeng X

Yonsei medical journal 20190301 3

<h4>Purpose</h4>Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently, microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanisms of miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration, invasion, and epithelial-mesenchymal transition (EMT).<h4>Materials and methods</h4>We investigated the key roles and possib ...[more]

PMID: 30799589

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Project description:Metastasis is responsible for the rapid recurrence and poor survival of malignancies. Epithelial-mesenchymal transition (EMT) has a critical role in metastasis. Increasing evidence indicates that EMT can be regulated by microRNAs (miRNAs). The aim of this study was to investigate the role of miR-26b in modulating epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC), as well as to identify its underlying mechanism of action.The expression level of miR-26b was assessed in multiple HCC cell lines (HepG2, MHCC97H, Hep3B, MHCC97L, HCCC9810, BEL-7402, Huh7 and QGY-7703), as well as in liver tissue from patients with HCC. Follow-up studies examined the effects of a miR-26b mimic (increased expression) and a miR-26b inhibitor (decreased expression) on markers of EMT, wound healing and cell migration. The molecular target of miR-26b was also identified using a computer algorithm and confirmed experimentally.MiR-26b expression was decreased in HCC cell lines and was inversely correlated with the grade of HCC. Increased expression of miR-26b inhibited the migration and invasiveness of HCC cell lines, which was accompanied by decreased expression of the epithelial marker E-cadherin and increased expression of the mesenchymal marker vimentin, at both the mRNA and protein expression levels. A binding site for miR-26b was theoretically identified in the 3'UTR of USP9X. Further studies revealed that overexpression of miR-26b repressed the endogenous level of USP9X protein expression. Overexpression of miR-26b also repressed Smad4 expression, whereas its inhibition elevated Smad4 expression.Taken together, our results indicate that miR-26b were inhibited in HCC. In HCC cell lines, miR-26b targeted the 3'UTR of USP9X, which in turn affects EMT through Smad4 and the TGF-? signaling pathway. Our analysis of clinical HCC samples verifies that miR-26b also targets USP9X expression to inhibit the EMT of hepatocytes. Thus, miR-26b may have some effects on the EMT of HCC cells.

Project description:PurposeThe aim of this work was to investigate the clinicopathological significance of fibrinogen gamma chain (FGG) and its biological roles during hepatocellular carcinoma (HCC) development and progression.MethodsThe expression of FGG was examined by Western blot and reverse transcription quantitative PCR in two different sample sets, including 24 or 35 pairs of HCC tumor tissues and their corresponding adjacent non-tumorous tissues. Afterward, association analysis between the expression of FGG and clinicopathological characteristics was systematically analyzed in 79 HCC patients. Subsequently, the mobility and invasiveness of SK-HEP-1 cells with FGG overexpression or knockdown were evaluated by transwell assay and wound healing assay. Additionally, the expressions of epithelial to mesenchymal transition (EMT)-associated markers were also detected in FGG overexpressed or silenced SK-HEP-1 cells.ResultsThe expression of FGG was significantly increased in primary HCC tissues comparing with its corresponding adjacent non-tumorous tissues. Clinical pathological analysis demonstrated that upregulation of intracellular FGG was significantly associated with increased vascular invasion, more satellite nodules, and more advanced TNM stage, and HCC patients with stronger expression of FGG had a higher recurrence rate and correspondingly a shorter overall survival time. Meanwhile, the high expression of FGG was also proved to be an independent risk factor for disease-free survival after surgical resection. In vitro phenotype studies showed that overexpression of FGG could promote the migration and invasion in SK-HEP-1 cells; conversely, these phenotypes could be significantly inhibited by knocking down the expression of FGG. Mechanism studies indicated that FGG could promote the migration and invasion through EMT signaling pathway by regulating the expressions of Slug and ZEB1.ConclusionFGG played important roles in enhancing cancer cell motility and invasiveness through EMT signaling, and might serve as a potential prognostic biomarker for HCC patients.

Dataset Information

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1.

Purpose

Materials and methods

Results

Conclusion

Publications

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1.

Similar Datasets

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