RETRACTED ARTICLE: Integrin-β5, a miR-185-targeted gene, promotes hepatocellular carcinoma tumorigenesis by regulating β-catenin stability

Lin, Zhikun; He, Ruiping; Luo, Haifeng; Lu, Chao; Zhang, Ning; Wu, Yuanhang; Han, Chuanchun; Tan, Guang; Wang, Zhongyu

doi:10.1186/s13046-018-0691-9

Cited by 51 publications

(40 citation statements)

References 38 publications

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“…In this study, the mechanism of DC-SIGN upregulation in CRC was mainly elucidated in the following two aspects. First, we found miR-185 targets DC-SIGN mRNA by binding to the DC-SIGN 3′-UTR to downregulate DC-SIGN expression, which confirmed previous findings that miR-185 regulates gene expression by initiating mRNA degradation and functions as a tumor suppressor [26,27]. We also found that the low miR-185 expression level was associated with CRC metastasis.…”

Section: Discussionsupporting

confidence: 89%

“…According to the datasets, we noticed that miR-185 is frequently downregulated in CRC and appears to be a promising biomarker [25]. miR-185 is involved in the suppression of the malignant process, especially tumor metastasis [26,27]. Several studies have documented that miRNAs frequently form feedback loops since they themselves are regulated by transcription factors that may, in turn, target directly or indirectly [28,29].…”

Section: Introductionmentioning

confidence: 99%

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DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis

Yuan

Zhang

et al. 2019

Cell Death Differ

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DC-SIGN is previously focused on its physiologic and pathophysiologic roles in immune cells. Little is known about whether DC-SIGN is expressed in malignant epithelial cells and how DC-SIGN participates in tumor progression. Here we showed that DC-SIGN expression was increased in metastatic colorectal cancer (CRC) cell lines and patient tissues. The overall survival in CRC patients with positive DC-SIGN was remarkably reduced. Gain of DC-SIGN function facilitated the CRC metastases both in vitro and in vivo, and this effect was reversed by miR-185. DC-SIGN and Lyn interacted physically, and Lyn maintained the stability of DC-SIGN in cells. DC-SIGN activation recruited Lyn and p85 to form the DC-SIGN-Lyn-p85 complex, which promoted CRC metastasis by increasing PI3K/Akt/β-catenin signaling in tyrosine kinase Lyndependent manner. Furthermore, activation of DC-SIGN promoted the transcription of MMP-9 and VEGF by increasing PI3K/Akt/β-catenin signaling, and induced TCF1/LEF1-mediated suppression of miR-185. Our findings reveal the presence of the DC-SIGN-TCF1/LEF1-miR-185 loop in cancer cells with metastatic traits, implying that it may represent a new pathogenic mechanism of CRC metastasis. This character of the loop promises to provide new targets for blocking CRC invasive and metastatic activity.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis

Yuan

Zhang

et al. 2019

Cell Death Differ

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“…Integrins are heterodimeric cell surface receptors composed of α-subunits and 8 β-subunits, and modulate a variety of biological functions in tumorigenesis [20]. As previously described, ITGB1 is considered as a key adhesion receptor for ECM components and can contribute to cell proliferation, invasion and metastasis in various cancers [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…ITGB1 is crucial for fascin-mediated breast cancer stem cell function and disease progression [24]. Lin et al demonstrated that miR-185/ITGB5 played an essential role in the development of HCC through mediating β-catenin pathway [25]. In breast cancer cells, the tumorigenic ability could be facilitated due to the ITGB5mediated EMT induced by transforming growth factor β [26].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel candidate biomarkers and efficacious small molecule drugs for pancreatic adenocarcinoma based on comprehensive bioinformatics technology

Yang¹,

Wang²,

Li³

2020

Preprint

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Background: Pancreatic adenocarcinoma (PAAD) is considered as one of most serious solid tumors with high mortality as well as incidence. We performed this present study to screen out novel biomarkers and potential efficacious small drugs in PAAD using integrated bioinformatics analyses. Methods: Expression profiles derived from TCGA and GTEx datasets were integrated by following bioinformatics methods: DEGs analysis, WGCNA, KEGG and GO enrichment analyses. Kaplan-Meier method was conducted to assess the prognostic performance of genes, and the predictive value of identified genes was determined by the ROC analysis. CMap analysis was utilized to identify the related small molecule drugs in PAAD. Results: A total of 4777 DEGs containing 2536 up-regulated and 2241 down-regulated genes were identified. WGCNA identified six modules that were related with clinical characteristics, and functional enrichment analyses showed that all genes of blue module were enriched in EMT, PI3K/Akt signaling pathway and other important biological processes and pathways. Moreover, three genes ( ITGB1 , ITGB5 , and OSMR ) of blue module were determined as key genes with higher expression levels and significant prognostic value. ROC analysis revealed that these three genes had excellent diagnostic efficiency for PAAD. These three key genes were highly regulated in PAAD tissues compared with normal controls. A panel of small molecule drugs including thapsigargin, viomycin, adiphenine, and CP-690334-01 were screened out to treat PAAD. Conclusion: In conclusion, our findings identified three key genes implicated in PAAD and screened out several potential small drugs to treat it, which may shed novel insights into the development of PAAD and its treatment.

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“…Recently, Hoshino et al proved that exosomal β5 integrin regulates liver tropism associated with liver metastasis in several tumors [ 12 , 13 , 24 ]. In a more recent study, Lin et al demonstrated that β5 integrin is highly expressed in HCC tissues, facilitating cancer cell growth and promoting cell migration [ 25 ]. In human HCC patients, fibrinogen [ 26 ] activates hepatic stellate cells (HSC) [ 27 ] and liver specific mesenchymal cells by binding αvβ5 integrin [ 28 ] widely expressed by neoplastic cells to promote liver disease progression and tumor metastasis [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide

et al. 2020

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Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without ‘off-target’ protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma.

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RETRACTED ARTICLE: Integrin-β5, a miR-185-targeted gene, promotes hepatocellular carcinoma tumorigenesis by regulating β-catenin stability

Cited by 51 publications

References 38 publications

DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis

DC-SIGN–LEF1/TCF1–miR-185 feedback loop promotes colorectal cancer invasion and metastasis

Identification of novel candidate biomarkers and efficacious small molecule drugs for pancreatic adenocarcinoma based on comprehensive bioinformatics technology

Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide

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