ING4 suppresses hepatocellular carcinoma via a NF-κB/miR-155/FOXO3a signaling axis

Qian, Fuliang; Hu, Qingqing; Tian, Yali; Wu, Jie; Li, Dapeng; Tao, Min; Qin, Lei; Shen, Bairong; Xie, Yufeng

doi:10.7150/ijbs.28422

Cited by 38 publications

(30 citation statements)

References 60 publications

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“…Recent studies have revealed that miRNAs including the miR-200 family regulate the metastasis by enhancing E-cadherin expression and inhibiting EMT [ 25 ]. miR-155 fosters cell migration and invasion in HCC cells via targeting the Ras homolog gene family member A (RhoA) [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-587 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Targeting Ribosomal Protein SA

Chen

Wang

Liu

et al. 2020

BioMed Research International

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Background. Hepatocellular carcinoma (HCC) is one of the most highly aggressive cancer worldwide with an extremely poor prognosis. Evidence has revealed that microRNA-587 (miR-587) is abnormally expressed in a series of cancers. However, its expressions and functions in HCC have not been clearly acknowledged. Methods. We detected the expression level of miR-587 both in the Gene Expression Omnibus (GEO) database and 86 paired clinical HCC tissues together with paired adjacent normal tissues by quantitative real-time PCR (qRT-PCR). Afterwards, the transfected HCC cell line SMMC-7721 cells were collected for the cell proliferation assay, cell-cycle arrest, cell migration, and invasion assays to explore the roles of miR-587 in regulating cellular function. In addition, bioinformatics analysis, combined with qRT-PCR and dual-luciferase reporter assays, were performed to confirm whether ribosomal protein SA (RPSA) mRNA was the direct target gene of miR-587. Moreover, the Cancer Genome Atlas (TCGA) and GEO databases as well as 86 paired clinical HCC tissues were used to verify the negative regulation between miR-587 and RPSA. Results. In the present study, both the GEO database (GSE36915 and GSE74618) analysis and qRT-PCR analysis of 86 paired clinical tissues showed that miR-587 was significantly downregulated in HCC tissues. The overexpression of miR-587 inhibited proliferation, cell cycle, migration, and invasion in SMMC-7721 cells. In addition, miR-587 directly interacted with the 3′-untranslated region (UTR) of RPSA. Moreover, miR-587 overexpression directly suppressed RPSA expression, and the two genes were inversely expressed in HCC based on the analyses in TCGA and GEO (GSE36376) databases and qPCR analysis of 86 paired clinical tissues. Conclusion. Our results demonstrate that miR-587 is downexpressed in HCC and regulates the cellular function by targeting RPSA.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-587 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Targeting Ribosomal Protein SA

Chen

Wang

Liu

et al. 2020

BioMed Research International

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“…The results showed that bevacizumab could upregulate ING4, promote cell apoptosis and inhibit cell activity. The increase of ING4 can promote the downstream NF-κB and FoxO3 apoptosis pathways (11,12), so the increase of ING4 is the direct cause of the increase of cell apoptosis rate. In this study, the downregulation of caspase-3, Bax and β-catenin expression and the increase of apoptosis rate in colon cancer cells after knockout of ING4 also prove that ING4 can induce apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Ma et al (11) found that the inhibitory effect of ING4 on melanoma can be realized by activating Fas/caspase-8 apoptosis pathway. Qian et al (12) believed that ING4 can inhibit the growth and metastasis of liver cancer tumor by inhibiting NF-κB and upregulating FoxO3. ING4 plays an important role in colon cancer.…”

Section: Introductionmentioning

confidence: 99%

Effect of bevacizumab on expression level of GLI1 and ING4 in colon cancer animal model

Suo

Mei

2020

Oncol Lett

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This study aimed to investigate the effect of bevacizumab on GLI1 and ING4 expression in colon cancer animal model. Colon cancer model in rats was induced by azoxymethane (AOM). Bevacizumab was used for the treatment of colon cancer rats. Tumor volume and weight were measured, tumor growth curve was visualized and tumor inhibition rate was calculated. GLI1 and ING4 of colon cancer cells were silencing expressed. Western blot analysis was used to detect the expressions of GLI1, ING4, caspase-3, Bax, β-catenin, Bcl2, PTEN, PI3K, Akt, NF-κB. The apoptosis rate was detected by flow cytometry. MTT assay was used to detect cell activity to get IC 50 value. After AOM induced colon cancer model in rats, the expressions of ING4, caspase-3, Bax and PTEN were downregulated, the expressions of GLI1, β-catenin, Bcl2, PI3K, Akt and NF-κB were upregulated and the apoptosis rate was downregulated. After bevacizumab treatment, the tumor volume and weight decreased, the expressions of ING4, caspase-3, Bax, PTEN were upregulated, the expressions of GLI1, β-catenin, Bcl2, PI3K, Akt, NF-κB were downregulated, and the cell apoptosis rate increased. Cell experiments showed that GLI1 promotes tumor growth and reduces the sensitivity of bevacizumab, while ING4 inhibits tumor growth and increases the sensitivity of bevacizumab. Bevacizumab inhibits the growth of colon cancer tumor by upregulating ING4 and downregulating GLI1. Materials and methods AOM-induced colon cancer model in rats. SD male rats were randomly divided into control group, sham operation group,

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“…The prepared 3 µm-thick human lung cancer TMA section was subjected to IHC analysis of SIRT7 using rabbit anti-SIRT7 (1:50) primary antibody and HRP-conjugated anti-rabbit IgG (1:1,000) secondary antibody as previously described ( 31 ). SIRT7 expression level of each specimen was evaluated by a weighted IHC score (0-1, -; 2–3, +; 4–5, ++; and 6–7, +++) ( 31 ). A weighted score of ≥4 (++ or +++) was considered as SIRT7 high expression in a tissue specimen.…”

Section: Methodsmentioning

confidence: 99%

Sirtuin 7 promotes non‑small cell lung cancer progression by facilitating G1/S phase and epithelial‑mesenchymal transition and activating AKT and ERK1/2 signaling

et al. 2020

Self Cite

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Increasing evidence has indicated the roles of sirtuin 7 (SIRT7) in numerous human cancers. However, the effects and the clinical significance of SIRT7 in human lung cancer is largely unknown. The present research demonstrated that SIRT7 was increased in human lung cancer tumor tissues. SIRT7 upregulation was associated with clinicopathological characteristics of lung cancer malignancy including positive lymph node metastasis, high pathologic stage and large tumor size. SIRT7 was also upregulated in human non-small cell lung cancer (NSCLC) cell lines. Furthermore SIRT7-overexpressed A549 (A549-SIRT7) and SIRT7-knocked down H292 (H292-shSIRT7) human NSCLC cell lines were established. Using these NSCLC cells and xenograft mouse models, it was revealed that SIRT7 overexpression markedly promoted growth and G1 to S cell cycle phase transition as well as migration, invasion and distant lung metastasis in A549 NSCLC cells, whereas SIRT7 knockdown suppressed these processes in H292 NSCLC cells. Mechanistically, in A549 NSCLC cells, SIRT7 overexpression significantly activated not only protein kinase B (AKT) signaling but also extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. SIRT7 overexpression also significantly downregulated cyclin-dependent kinase (CDK) inhibitors including p21 and p27 as well as upregulated cyclins including cyclin D1 and cyclin E1, and CDKs including CDK2 and CDK4. Notably, the epithelial-mesenchymal transition (EMT) process of A549 NSCLC cells was facilitated by SIRT7 overexpression, as evidenced by E-cadherin epithelial marker downregulation and mesenchymal markers (N-cadherin, vimentin, Snail and Slug) upregulation. In addition, SIRT7 knockdown in H292 NSCLC cells exhibited the opposite regulatory effects. Moreover, inhibition of AKT signaling abated the promoting effects of SIRT7 in NSCLC cell proliferation and EMT progression. The present data indicated that SIRT7 accelerated human NSCLC cell growth and metastasis possibly by promotion of G1 to S-phase transition and EMT through modulation of the expression of G1-phase checkpoint molecules and EMT markers as well as activation of AKT and ERK1/2 signaling. SIRT7 could be an innovative potential target for human NSCLC therapy.

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ING4 suppresses hepatocellular carcinoma via a NF-κB/miR-155/FOXO3a signaling axis

Cited by 38 publications

References 60 publications

MicroRNA-587 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Targeting Ribosomal Protein SA

MicroRNA-587 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Targeting Ribosomal Protein SA

Effect of bevacizumab on expression level of GLI1 and ING4 in colon cancer animal model

Sirtuin 7 promotes non‑small cell lung cancer progression by facilitating G1/S phase and epithelial‑mesenchymal transition and activating AKT and ERK1/2 signaling

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