Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma

Meng, Jing; Liu, Yanrong; Han, Jing; Tan, Qiang; Chen, Shuang; Qiao, Kun; Zhou, Honggang; Sun, Tao; Yang, Cheng

doi:10.1186/s12943-017-0640-9

Cited by 53 publications

(42 citation statements)

References 32 publications

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“…The secondary antibody was subsequently added using an horseradish peroxidase-polymer anti-mouse/ rabbit IHC kit (Maixin Biotech) for 1 hour at room temperature. Then, the samples were developed with diaminobenzidine reagent, counterstained with hematoxylin and mounted with permount (33). The immunohistochemistry score was calculated by multiplying the intensity (0 ¼ negative, 1 ¼ canary yellow, 2 ¼ claybank, 3 ¼ brown) and the positive cell percentage scores (1 ¼ less than 25%, 2 ¼ 25% to 50%, 3 ¼ 51% to 75%, 4 ¼ more than 75%).…”

Section: Ihc Assay and Analysismentioning

confidence: 99%

Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

et al. 2018

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Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1 and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies. A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC. http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg .

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Section: Ihc Assay and Analysismentioning

confidence: 99%

Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

et al. 2018

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“…Furthermore, HSP90 interacts with and inhibits the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme of mevalonate pathway that is essential for cancer progression [74]. Since HSP90 serves to promote the transcription and expression of vascular endothelial growth factor receptors (VEGFRs), the major receptors involved in endothelial cell-dependent tumor angiogenesis, HSP90 overexpression leads to the enhanced proliferation, migration, invasion, and tube cell-dependent tumor angiogenesis in vitro and in vivo [75]. In breast cancer, increased levels of HSP90 are often detected, and HSP90 functions to stabilize the heightened activation of estrogen receptor (ErbB)-dependent PI3K/AKT and ERK signaling pathways.…”

Section: Role Of Hsp90 In Cancer Developmentmentioning

confidence: 99%

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Yun

Kim

Lim

et al. 2019

Cells

209

158

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Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in protein folding and maturation processes under diverse stressors such as heat shock, hypoxia, and degradation. Notably, HSPs also play essential roles across cancers as they are implicated in a variety of cancer-related activities such as cell proliferation, metastasis, and anti-cancer drug resistance. In this review, we comprehensively discuss the functions of HSPs in association with cancer initiation, progression, and metastasis and anti-cancer therapy resistance. Moreover, the potential utilization of HSPs to enhance the effects of chemo-, radio-, and immunotherapy is explored. Taken together, HSPs have multiple clinical usages as biomarkers for cancer diagnosis and prognosis as well as the potential therapeutic targets for anti-cancer treatment.

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“…Hsp90β plays an important role in the growth and proliferation of tumors [26]. Recent study have revealed that Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma [27]. Moreover, studies have shown that Hsp90β is highly expressed in glioma tissue, and its inhibitors can inhibit the migration and invasion of glioma cells and inhibit the secretion of vascular endothelial growth factor [28].…”

Section: Introductionmentioning

confidence: 99%

MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change

Zhao

Liu

et al. 2019

J Exp Clin Cancer Res

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BackgroundRNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs).MethodsThe expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR. The expressions of MOV10, ZIC4, Hsp90 and PI3K/Akt were detected by real-time PCR or western blot. The binding ability of circ-SHKBP1 and miR-544a / miR-379, ZIC4 and miR-544a / miR-379 were analyzed with Dual-Luciferase Reporter System or RIP experiment. The direct effects of ZIC4 on the Hsp90β promoter were analyzed by the ChIP experiment. The cell viability, migration and tube formation in vitro were detected by CCK-8, Transwell assay and Matrigel tube formation assay. The angiogenesis in vivo was evaluated by Matrigel plug assay. Student’s t-test (two tailed) was used for comparisons between two groups. One-way analysis of variance (ANOVA) was used for multi-group comparisons followed by Bonferroni post-hoc analysis.ResultsThe expressions of RNA binding proteins MOV10, circ-DICER1, ZIC4, and Hsp90β were up-regulated in GECs, while miR103a-3p/miR-382-5p were down-regulated. MOV10 binding circ-DICER1 regulated the cell viability, migration, and tube formation of GECs. And the effects of both MOV10 and circ-DICER1 silencing were better than the effects of MOV10 or circ-DICER1 alone silencing. In addition, circ-DICER1 acts as a molecular sponge to adsorb miR-103a-3p / miR-382-5p and impair the negative regulation of miR-103a-3p / miR-382-5p on ZIC4 in GECs. Furthermore, ZIC4 up-regulates the expression of its downstream target Hsp90β, and Hsp90 promotes the cell viability, migration, and tube formation of GECs by activating PI3K/Akt signaling pathway.ConclusionsMOV10 / circ-DICER1 / miR-103a-3p (miR-382-5p) / ZIC4 pathway plays a vital role in regulating the angiogenesis of glioma. Our findings not only provides novel mechanisms for the angiogenesis of glioma, but also provide potential targets for anti-angiogenesis therapies of glioma.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0990-1) contains supplementary material, which is available to authorized users.

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Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma

Cited by 53 publications

References 32 publications

Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change

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