Dataset Information

Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway.

ABSTRACT:

Background

Elevated level of interleukin-8 (IL-8) promotes hepatocellular carcinoma (HCC) development and contributes to poor prognosis. Previously, we have proved that Dicer inhibits HCC progression. In this study, we evaluated the potential interaction between IL-8 and Dicer as well as their influence on HCC.

Methods

Hepatocellular carcinoma cells of SMMC-7721 were divided into 2 groups for subsequent analysis: pCMV-Dicer group for Dicer-overexpressing lentivirus transfected cells (pCMV-Dicer cells) and pCMV-NC group for empty lentivirus transfected cells (pCMV-NC cells). Cell Counting kit-8 (CCK8), wound healing, and transwell were used to evaluate the inhibitory effect of Dicer overexpression on proliferation, migration, and invasion of HCC cells. The level of IL-8 was measured by flow cytometry bead-based immunoassays. Male nude BALB/c mice injected with pCMV-Dicer or pCMV-NC cell suspensions was used for transplant of HCC tumor.

Results

We found that the secretion of IL-8 was reduced in the medium of pCMV-Dicer cells (P = .027). Recombinant human IL-8 (rhIL-8) reversed the inhibitory effect of Dicer on proliferation (P < .01), migration (P = .003), and invasion (P = .001), whereas IL-8 inhibitor of reparixin enhanced inhibitory effect of Dicer on proliferation (P < .05), migration (P = .008), and invasion (P = .000). Lenvatinib downregulated the IL-8 level of HCC cells (P = .000) as well as promote Dicer-induced inhibition for HCC cells referring to proliferation (P < .05), migration (P = .000), and invasion (P = .000). Animal experiments also demonstrated that Dicer cooperated with lenvatinib to inhibit the growth of HCC tumors (P < .05).

Conclusions

Dicer cooperated with lenvatinib to inhibit HCC growth via downregulating IL-8, and Dicer displayed its potential capability to enhance the anti-tumor effect of lenvatinib.

SUBMITTER: Han X

PROVIDER: S-EPMC10088407 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway.

Han Xin X Wu Jianhua J Sha Ziyue Z Lai Ruixue R Shi Jianfei J Mi Lili L Yin Fei F Guo Zhanjun Z

Clinical Medicine Insights. Oncology 20230407

<h4>Background</h4>Elevated level of interleukin-8 (IL-8) promotes hepatocellular carcinoma (HCC) development and contributes to poor prognosis. Previously, we have proved that Dicer inhibits HCC progression. In this study, we evaluated the potential interaction between IL-8 and Dicer as well as their influence on HCC.<h4>Methods</h4>Hepatocellular carcinoma cells of SMMC-7721 were divided into 2 groups for subsequent analysis: pCMV-Dicer group for Dicer-overexpressing lentivirus transfected cel ...[more]

PMID: 37056297

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Project description:BackgroundAbnormal expression of Fanconi anaemia complementation group I (FANCI) has been implicated in carcinogenesis. However, the precise role of FANCI in the development of hepatocellular carcinoma (HCC) remains unclear.Materials & methodsWe conducted a comprehensive bioinformatics analysis of FANCI's role based on HCC patient sequencing data in the TCGA and GEO databases. Then, we performed qPCR, Western blotting (WB), and immunohistochemistry (IHC) assays. SiRNA-mediated knockdown of FANCI was conducted, followed by CCK-8, EdU staining, and colony formation experiments to evaluate the impact of FANCI knockdown on HCC cell behaviour. Flow cytometry was employed to explore alterations in the cell cycle after FANCI knockdown in HCC cell lines. Furthermore, RNA sequencing was performed to investigate potential mechanisms following FANCI knockdown, and WB analysis was used to validate the corresponding pathway.ResultsOur bioinformatics analysis revealed elevated expression of FANCI in HCC, which was subsequently validated through qPCR, WB, and IHC assays. High expression of FANCI was significantly associated with a poor prognosis in HCC patients. Univariate and multivariate Cox regression analyses identified FANCI as an independent prognostic risk factor for HCC patients. Additionally, the coexpressed genes of FANCI were found to be associated with multiple cancer pathways. Knockdown of FANCI expression significantly inhibited HCC cell proliferation and colony formation by inducing cell cycle arrest. Further WB analysis revealed that FANCI knockdown suppressed the expression of Cyclin D1 and p-AKT while increasing the expression of GSK-3β in HCC cells. However, no significant differences were observed in the expression levels of AKT and PI3K.ConclusionOverall, our research provides substantial proof of FANCI's crucial function as an oncogene in HCC. It could serve as a potential prognostic marker, therapeutic target, and tumorigenic factor in HCC.

Dataset Information

Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway.

Background

Methods

Results

Conclusions

Publications

Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway.

Similar Datasets

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