Targeting Signalling Pathways in Hepatocellular carcinoma

Blagotinsek, Kaja; Rozman, Damjana

doi:10.2174/1381612822666161006160005

Cited by 24 publications

(23 citation statements)

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“…Pathway analysis from KEGG and Panther demonstrated that tight junction and Wnt signaling pathway are among the most relevant pathways for HCC. Tight junction signaling contributes to pathogenesis of GC and CRC, plays functional roles in epithelial-to-mesenchymal transition and viral entry, and could be used as potential targets for gastrointestinal and liver disease; while Wnt signaling pathway is well known to impact on hepatocarcinogenesis and HCC progression [42][43][44][45]. These results suggested that these DECs may participate in HCC progression by regulating their parental genes.…”

Section: Discussionmentioning

confidence: 94%

Circular RNA Signature in Hepatocellular Carcinoma

Qiu¹,

Wang²,

Ge³

et al. 2019

J. Cancer

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Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Circular RNAs (circRNAs) are a new class of endogenous functional non-coding RNAs (ncRNAs), and have been demonstrated to play important roles in the development of HCC. This study aimed to explore the significance of circRNAs in HCC progression. HCC-associated circRNA expression profiles GSE94508 and GSE97332 were downloaded from the Gene Expression Omnibus database (GEO), and 87 differentially expressed circRNAs (DECs) between HCC tissues and paired non-cancer tissues were identified, including 76 up-regulated and 11 down-regulated circRNAs. Gene ontolog (GO) and pathway analyses of the host genes of these DECs suggested that these host genes were enriched in cell adhesion, cytosol, and protein binding, and were associated with tight junction and Wnt signaling pathways. CircRNA-miRNA interaction prediction identified 20 miRNAs that predispose to interact with DECs. Among these, four essential miRNAs, hsa-miR-7-5p, hsa-miR-145-5p, hsa-miR-203a-3p, and hsa-miR-192-5p, were reported to play pivotal roles in HCC progression by targeting multiple genes. Pathway analysis suggested that putative target genes of these essential miRNAs were involved in HCC-associated signaling pathways, such as Wnt, TGF-β, and Ras; whereas protein-protein network (PPI) analysis demonstrated that some validated target genes of these miRNAs, such as PIK3CA, AKT1, MYC, JUN, SMAD4, and SRC, were hub target genes as they have more counts of interacting protein. In the meantime, the deregulation of some DECs was validated in HCC cell line HepG2 compared with normal liver cell line L02 by quantitative real-time polymerase chain reaction (qRT-PCR) and the Sanger sequencing. This study identified a set of DECs in HCC, and provided a comprehensive understanding of the roles of these DECs in HCC progression.

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Section: Discussionmentioning

confidence: 94%

Circular RNA Signature in Hepatocellular Carcinoma

Qiu¹,

Wang²,

Ge³

et al. 2019

J. Cancer

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“…Like all other types of cancers, the onset and progression of HCC is driven by various signaling pathways, including Wnt-βcatenin, Hedgehog, Raf/MEK/ERK, Met-HGF, and so forth. 28,29 Among which, mTOR signaling was selected for further exploration of the mechanism of HEIH, since it has been widely reported as a downstream signaling of F I G U R E 5 Effects of HEIH silence together with miR-199a-3p suppression on Hep3B cells growth and metastasis. A, miR-199a-3p expression was tested by qRT-PCR, after Hep3B cells were transfected with miR-199a-3p inhibitor or NC.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Silence of lncRNA HEIH suppressed liver cancer cell growth and metastasis through miR‐199a‐3p/mTOR axis

Cao

et al. 2019

J of Cellular Biochemistry

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Background/Aims High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines. Methods The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied. Results As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl‐2, MMP‐2, MMP‐8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase‐3. MicroRNA (miR)‐199a‐3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR‐199a‐3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR‐199a‐3p. Conclusion HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR‐199a‐3p, and thereby blockage of mTOR signaling.

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“…With tumor tissues growing, one of the critical mediators of hypoxic responses is the hypoxia-inducible factor 1a (HIF-1a). Increasing evidence have demonstrated that the activation of PI3K/AKT signaling pathway elevates VEGF expression by up-regulating HIF-1a Blagotinsek and Rozman, 2017;Kim et al, 2017). Thus, identification of drugs that inhibit PI3K/AKT signaling pathway and decrease VEGF and HIF-1a expression is instructive for treating HCC.…”

Section: Introductionmentioning

confidence: 99%

Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression

Ren

Yang

et al. 2020

Front. Pharmacol.

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Recent studies have revealed that natural plants-derived polysaccharides exhibit potent anti-tumor activity. Our earlier studies suggest that dandelion polysaccharide (DP) inhibits hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo. Here, we investigated the effects of DP on the angiogenesis of HCC and the potential molecular mechanisms by which DP regulates angiogenesis. Wound-healing and transwell invasion assays revealed that DP inhibited HUVECs migration and invasion in vitro, respectively. Tube formation assay, chick chorioallantoic membrane (CAM) assay, and immunohistochemistry (IHC) demonstrated that DP suppressed vasculogenesis in vitro and in vivo. Moreover, Western blot and immunofluorescence staining verified that DP treatment decreased the protein levels of some key factors involved in angiogenesis of HCC, such as hypoxia-inducible factor 1a (HIF-1a), vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT. However, activation of PI3K/AKT pathway with insulin-like growth factor 1 (IGF-1) treatment attenuated the effect of DP on angiogenesis via lowering the expression of HIF-1a and VEGF. In summary, we found that DP treatment inhibited angiogenesis in vivo and in vitro through suppressing expression of VEGF and HIF-1a. Furthermore, we showed that the expression of VEGF and HIF1-a was modulated by PI3K/AKT signaling. Collectively, our study suggests that DP is a promising anti-cancer drug candidate for treating HCC.

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Targeting Signalling Pathways in Hepatocellular carcinoma

Abstract: This review reveals that oncogenes, especially microRNAs that are conserved across species and interfere with signalling pathways might be used as promising strategies for halting or reversing the progression of HCC.

Cited by 24 publications

References 0 publications

Circular RNA Signature in Hepatocellular Carcinoma

Circular RNA Signature in Hepatocellular Carcinoma

Retracted: Silence of lncRNA HEIH suppressed liver cancer cell growth and metastasis through miR‐199a‐3p/mTOR axis

Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression

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