RIG-I suppresses the migration and invasion of hepatocellular carcinoma cells by regulating MMP9

Liu, Zhikui; Dou, Changwei; Jia, Yuli; Li, Qing; Zheng, Xin; Yao, Yingmin; Liu, Qingguang; Song, Tao

doi:10.3892/ijo.2015.2853

Cited by 35 publications

(30 citation statements)

References 34 publications

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“…MMP 9 is a metalloproteinase that facilitates the detachment of cancer cells from the primary tumor and the later extravasation at the secondary site. [20] Dynamic expressions of MMP 9 and other proteinases were reported to regulate the early invasion of HCC. [21] Studies also suggested that MMP 9 would serve as a prognostic marker for the risk of metastasis in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2

Zhou

Yang

et al. 2016

Chinese Medical Journal

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Background:Decoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2.Methods:HepG2 cells were stably transfected with lentivirus-based short hairpin RNA vector targeting DcR3. After the knockdown of DcR3 was confirmed, cell proliferation, clone formation, ability of migrating across transwell membrane, and wound healing were assessed in vitro. Matrix metalloproteinase-9 (MMP 9) and vascular epithelial growth factor (VEGF)-C and D expressions of the DcR3 knockdown were also studied. Comparisons between multiple groups were done using one-way analysis of variance (ANOVA), while pairwise comparisons were performed using Student's t test. P < 0.05 was regarded statistically significant.Results:DcR3 was overexpressed in HepG2 compared to other HCC cell lines and normal hepatocyte Lo-2. Stable knockdown of DcR3 slowed down the growth of HepG2 (P < 0.05) and reduced the number of clones formed by 50% compared to those without DcR3 knockdown (P < 0.05). The knockdown also reduced the migration of HepG2 across transwell matrix membrane by five folds compared to the control (P < 0.05) and suppressed the closure of scratch wound (P < 0.05). In addition, the messenger RNA levels of MMP 9, VEGF-C, and VEGF-D were significantly suppressed by DcR3 knockdown by 90% when compared with the mock control (P < 0.05).Conclusions:Loss of DcR3 impaired the growth and invasive property of HCC cell line of HepG2. Targeting DcR3 may be a potential therapeutic approach for the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2

Zhou

Yang

et al. 2016

Chinese Medical Journal

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“…Thus, Xrn1 may not be the only cellular gene that targets the 5= terminus of the viral genome and may explain why Xrn1 knockdown alone is insufficient to restore replication to miR-122-bound levels (18,19,34). Given the RIG-I defect found in Huh7.5 cells but not Hep3B cells, it is unlikely that RIG-I signaling restricts HCV in the absence of miR-122 (38,39). Alternatively, miR-122 may have an additional function unrelated to end protection, such as in viral life cycle stages following translation, like the switch directing the viral genomic RNA to different functions (translation, transcription, packaging) or aiding in initiation of replication (40).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Hepatitis C Virus Genome Replication by Xrn1 and MicroRNA-122 Binding to Individual Sites in the 5′ Untranslated Region

Thibault

Huys

Amador-Cañizares

et al. 2015

J Virol

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miR-122 is a liver-specific microRNA (miRNA) that binds to two sites (S1 and S2) on the 5= untranslated region (UTR) of the hepatitis C virus (HCV) genome and promotes the viral life cycle. It positively affects viral RNA stability, translation, and replication, but the mechanism is not well understood. To unravel the roles of miR-122 binding at each site alone or in combination, we employed miR-122 binding site mutant viral RNAs, Hep3B cells (which lack detectable miR-122), and complementation with wild-type miR-122, an miR-122 with the matching mutation, or both. We found that miR-122 binding at either site alone increased replication equally, while binding at both sites had a cooperative effect. Xrn1 depletion rescued miR-122-unbound fulllength RNA replication to detectable levels but not to miR-122-bound levels, confirming that miR-122 protects HCV RNA from Xrn1, a cytoplasmic 5=-to-3= exoribonuclease, but also has additional functions. In cells depleted of Xrn1, replication levels of S1-bound HCV RNA were slightly higher than S2-bound RNA levels, suggesting that both sites contribute, but their contributions may be unequal when the need for protection from Xrn1 is reduced. miR-122 binding at S1 or S2 also increased translation equally, but the effect was abolished by Xrn1 knockdown, suggesting that the influence of miR-122 on HCV translation reflects protection from Xrn1 degradation. Our results show that occupation of each miR-122 binding site contributes equally and cooperatively to HCV replication but suggest somewhat unequal contributions of each site to Xrn1 protection and additional functions of miR-122. Hepatitis C virus (HCV) is a hepatotropic virus that infects an estimated 150 million humans worldwide, a significant portion of whom do not know their status due to the largely asymptomatic nature of the infection (1). The virus is transmitted by blood-to-blood contact, and humans are the only known reservoir. Chronic infection occurs in approximately 70% of cases and can lead to sequelae such as metabolic disease, steatosis, hepatocellular carcinoma, and decompensated liver disease late in infection (2).One of the major determinants of the virus' hepatotropism is its requirement for the liver-specific, liver-abundant miR-122 microRNA (miRNA) (3, 4). miR-122 binds to two sites at the 5= end of the virus' positive-sense RNA genome and has been shown to directly enhance viral RNA accumulation, since mutation of the miR-122 binding sites abolishes RNA accumulation, and the provision of exogenous miR-122 sequences that have compensatory mutations to restore binding also reinstates RNA accumulation (4-10). Argonaute-2, one of the key effector proteins in the microRNA pathway and a component of the RNA-induced silencing complex (RISC), binds in association with miR-122 and is required to increase HCV replication, while several other proteins in the microRNA pathway and RISC have been implicated in either the biogenesis or activity of miR-122 (5, 11-14). Although miR-122 uses canonical microRNA se...

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“…qRT‐PCR was performed as reported previously . Total RNA was extracted according to the protocol of TRIzol reagent (Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…qRT-PCR was performed as reported previously. 16,17 Total RNA was extracted according to the protocol of TRIzol reagent (Invitrogen, Carlsbad, CA, USA). qPCR primers against miR-1914 (HmiRQP0270), U6 (HmiRQP9001), GPR39 (HQP008237) and GAPDH (HQP006940) were obtained from GeneCopoeia (Guangzhou, China).…”

Section: Rna Extraction and Qrt-pcrmentioning

confidence: 99%

microRNA‐1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39‐mediated PI3K/AKT/mTOR pathway in HCC

Sun

Wang

Chen

et al. 2019

J Cellular Molecular Medi

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Increasing studies have confirmed that abnormally expressed microRNAs (miRNAs) take part in the carcinogenesis as well as the aggravation of hepatocellular carcinoma (HCC). However, little information is currently available about miR‐1914 in HCC. Here, we first confirmed that miR‐1914 inhibition in HCC cell lines and tumour specimens correlates with tumour size and histological grade. In a series of functional experiments, miR‐1914 inhibited tumour proliferation and colony formation, resulting in cell cycle arrest and increased apoptosis. Moreover, miR‐1914 mediated its functional effects by directly targeting GPR39 in HCC cells, leading to PI3K/AKT/mTOR repression. Restoring GPR39 expression incompletely counteracted the physiological roles of miR‐1914 in HCC cells. In addition, down‐regulation of AKT phosphorylation inhibited the effects of miR‐1914 in HCC. Furthermore, the overexpression of lncRNA DUXAP10 negatively correlated with the expression of miR‐1914 in HCC; thus, lncRNA DUXAP10 regulated miR‐1914 expression and modulated the GPR39/PI3K/AKT‐mediated cellular behaviours. In summary, the present study demonstrated for the first time that lncRNA DUXAP10–regulated miR‐1914 plays a functional role in inhibiting HCC progression by targeting GPR39‐mediated PI3K/AKT/mTOR pathway, and this miRNA represents a novel therapeutic target for patients with HCC.

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RIG-I suppresses the migration and invasion of hepatocellular carcinoma cells by regulating MMP9

Cited by 35 publications

References 34 publications

Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2

Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2

Regulation of Hepatitis C Virus Genome Replication by Xrn1 and MicroRNA-122 Binding to Individual Sites in the 5′ Untranslated Region

microRNA‐1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39‐mediated PI3K/AKT/mTOR pathway in HCC

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