scholarly journals Short-Chain Fatty Acid Butyrate Induces Cilia Formation and Potentiates the Effects of HDAC6 Inhibitors in Cholangiocarcinoma Cells

2022 ◽  
Vol 9 ◽  
Author(s):  
Kishor Pant ◽  
Seth Richard ◽  
Sergio A. Gradilone
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Synergistic Effects ◽  
Therapeutic Effects ◽  
Antitumor Effects ◽  
Cell Growth And Migration ◽  
Bacterial Fermentation ◽  
Cilia Formation ◽  
Butyrate Treatment ◽  
And Migration

Cholangiocarcinoma (CCA) is a deadly form of liver cancer with limited therapeutic approaches. The pathogenesis of CCA involves the loss of primary cilia in cholangiocytes, an important organelle that regulates several key cellular functions including the regulation of cell polarity, growth, and differentiation, by a mechanism involving increased expression of deacetylases like HDAC6 and SIRT1. Therefore, cilia restoration may represent an alternative and novel therapeutic approach against CCA. Butyrate is produced by bacterial fermentation of fibers in the intestine and has been shown to inhibit SIRT1, showing antitumor effects on various cancers. Herein, we investigated the role of butyrate on CCA cell proliferation, migration, and EMT and evaluated the synergistic effects with specific HDAC6 inhibition. When CCA cells, including HuCCT1 and KMCH, were treated with butyrate, the cilia formation and acetylated-tubulin levels were increased, while no significant effects were observed in normal human cholangiocytes. Butyrate treatment also depicted reduced cell proliferation in HuCCT1 and KMCH cells, but on the other hand, it affected cell growth of the normal cholangiocytes only at high concentrations. In HuCCT1 cells, spheroid formation and cell migration were also halted by butyrate treatment. Furthermore, we found that butyrate augmented the previously described effects of HDAC6 inhibitors on CCA cell proliferation and migration by reducing the expression of CD44, cyclin D1, PCNA, Zeb1, and Vimentin. In summary, butyrate targets cancer cell growth and migration and enhances the anti-cancer effects of HDAC6 inhibitors in CCA cells, suggesting that butyrate may have therapeutic effects in CCA and other ciliopathies.

miR-449b-5p Inhibits Cell Proliferation and Migration of Breast Cancer via Targeting Flotillin-2

2020 ◽  
Vol 10 (8) ◽  
pp. 1094-1101
Author(s):  
Delin Wu ◽  
Xiaopeng Ma
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Breast Carcinoma ◽  
Critical Role ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Cell Growth And Migration ◽  
Cancer Pathogenesis ◽  
And Migration

Background: MicroRNAs (miRNAs) act as a critical role in cancer pathogenesis, while the potential of miR-449b-5p in breast carcinoma remains to be fully inquired. Therefore, we purposed to probe the mechanism governing miR-449b-5p in breast cancer. Methods: Reverse transcription-PCR (RTPCR) was adopted to examine miR-449b-5p expression level in breast carcinoma. The functional experiments were implemented to estimate the role of miR-449b-5p in cell growth and migration. The interplay of miR-449b-5p with FLOT2 was validated with luciferase reporter assay. Results: miR-449b-5p level was markedly lessened in the tissue samples and cell lines of breast carcinoma. Overexpression of miR-449b-5p contributed to suppression of cell growth and migration whereas induced apoptosis in SKBr-3 and MCF-7 cells. Moreover, luciferase reporter experiment suggested that FLOT2 had a negative correlation with miR-449b-5p expression. Functionally, ectopic expression of FLOT2 reversed repressive effects of miR-449b-5p mimic on malignant behaviors of breast carcinoma cells. Conclusion: miR-449b-5p hindered cell proliferation, migration and facilitated cell apoptosis of breast carcinoma through targeting FLOT2. Our findings may offer a potent target for the therapy of breast carcinoma.

scholarly journals Down-regulated Long Noncoding RNAHOXA11-ASaffects trophoblast cell proliferation and migration by regulatingRND3andHOXA7expression in preeclampsia

2018 ◽  
Author(s):  
Yetao Xu ◽  
Dan Wu ◽  
Jie Liu ◽  
Zhonghua Ma ◽  
Bingqing Hui ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Noncoding Rna ◽  
Trophoblast Cell ◽  
Rna Seq ◽  
Biological Mechanisms ◽  
Aberrant Expression ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Proliferation And Migration

AbstractThe long noncoding RNAHOXA11-ASreveals abnormal expression in numerous human diseases. However, its function and biological mechanisms remain unclear in Preeclampsia (PE). In this study, we report thatHOXA11-ASwas significantly downregulated in preeclampsic placental tissues and could contribute to the occurrence and development of Preeclampsia. Silencing ofHOXA11-ASexpression could significantly suppress trophoblast cell growth and migration, whereasHOXA11-ASoverexpression facilitated cell growth in HTR-8/SVneo, JEG3 and JAR cell lines. RNA-seq analysis also indicated thatHOXA11-ASsilencing preferentially regulated numerous genes associated with cell proliferation and cell migration. Mechanistic analyses showed thatHOXA11-AScould recruit Ezh2 and Lsd1 protein, and regulateRND3mRNA expression in nucleus. In cytoplasm,HOXA11-ASmodulateHOXA7expression by sponged miR-15b-5p, thus affecting trophoblast cell proliferation. Together, these resulting data confirm that aberrant expression ofHOXA11-ASis involved in the occurrence and development of Preeclampsia, and may act as a prospective diagnosis and therapeutic target in PE.

scholarly journals The Inhibitory Effect of Sulforaphane on Bladder Cancer Cell Depends on GSH Depletion-Induced by Nrf2 Translocation

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4919
Author(s):  
Canxia He ◽  
Luigina P. Buongiorno ◽  
Wei Wang ◽  
Jonathan C. Y. Tang ◽  
Natalizia Miceli ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Inhibitory Effect ◽  
Bladder Cancer Cell ◽  
High Dose ◽  
Cell Growth And Migration ◽  
T24 Cells ◽  
And Migration

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. In this study, human bladder cancer T24 cells were used as in vitro model for revealing the inhibitory effect and its potential mechanism of SFN on cell growth. Here, a low dose of SFN (2.5 µM) was shown to promote cell proliferation (5.18–11.84%) and migration in T24 cells, whilst high doses of SFN (>10 µM) inhibited cell growth significantly. The induction effect of SFN on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression at both low (2.5 µM) and high dose (10 µM) was characterized by a bell-shaped curve. Nrf2 and glutathione (GSH) might be the underlying mechanism in the effect of SFN on T24 cell growth since Nrf2 siRNA and GSH-depleting agent L-Buthionine-sulfoximine abolished the effect of SFN on cell proliferation. In summary, the inhibitory effect of SFN on bladder cancer cell growth and migration is highly dependent on Nrf2-mediated GSH depletion and following production. These findings suggested that a higher dose of SFN is required for the prevention and treatment of bladder cancer.

scholarly journals Ramucirumab and GSK1838705A Enhance the Inhibitory Effects of Low Concentration Sorafenib and Regorafenib Combination on HCC Cell Growth and Motility

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 787 ◽  
Author(s):  
Rosalba D’Alessandro ◽  
Maria Grazia Refolo ◽  
Palma Aurelia Iacovazzi ◽  
Pasqua Letizia Pesole ◽  
Caterina Messa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Therapeutic Effects ◽  
Experimental Conditions ◽  
Cell Growth And Migration ◽  
Low Concentrations ◽  
And Migration ◽  
Endothelial Growth Factor

Several new multikinase inhibitors have recently been introduced into clinical practice for hepatocellular carcinoma (HCC) therapy. Small increases in survival were reported as well as considerable toxicity. There is thus a need for effective therapies with lower toxicities. We examined whether a combination of sorafenib and regorafenib might also be effective at very low concentrations, with resulting potential for lessened clinical toxicity. MTT test, clonogenic assay, Ki67 staining and cell cycle analysis were assessed for cell proliferation and Annexin V and western blotting analysis relative to the expression of cleaved Caspase-3 and BID for cell apoptosis. In these experimental conditions cell growth and migration were potently inhibited and apoptosis induced even in HCC cells producing high alpha fetoprotein (AFP) levels (clinically worse prognosis). The combination also inhibited levels of the two HCC biomarkers, AFP and des gamma carboxy prothrombin (DCP). Additional inhibition of Vascular Endothelial Growth Factor Receptor (VEGFR) or Insulin-like Growth Factor 1 Receptor (IGF1R) enhanced effects on AFP and DCP levels, cell growth inhibition and MAPK and PI3K/Akt signaling inhibition due to sorafenib/regorafenib combination. These combinations have the potential for decreased toxicity while simultaneously enhancing therapeutic effects. This potential decrease in toxicity is being explored in ongoing studies.

scholarly journals Hypoxia Induced HMMR Promotes the NSCLC Progression

2021 ◽  
Author(s):  
Duan Lin can ◽  
Jiang Xiu lin ◽  
Tan Lin ◽  
Yuan Yi xiao ◽  
Wang Juan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Poor Prognosis ◽  
High Expression ◽  
Related Gene ◽  
Cell Growth And Migration ◽  
Immune Infiltration ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Hyaluronan mediated motility receptor (also known as RHAMM) is another one of few defined hyaluronan receptors, play pivotal roles in cell growth. However, the functionof HMMR in lung adenocarcinoma remain unclear.Methods: HMMR expression was analyzed emoloyed the public databases, the prognosis of HMMR was analysis by prognoscan, KMplot and GEPIA databases. The GO and KEGG pathway was analysis by the DAVID and GSEA software. The correlation between the HMMR expression was analysis by the TIMER databases, the gene and protein networks was analysis by Genemania and STRING databases, the DNA methylation was analysis by the MethSurv and UALCAN databases. The expression of HMMR was analysis by IHC and qPCR, the function of HMMR on cell proliferation and migration was examine by the cell growth curve, clone information, transwell and wound healing assay.Results: in this study, we find that HMMR was elevated in LUAD and it’s highly expression associated with the poor prognosis and lymph node metastasis. Furthermore, the expression of HMMR was induced by hypoxia in LUAD. HMMR expression level not only positively correlation with the different immune cells, but also positively correlation with the expression of immune checkpoints related gene. Finally, depletion of HMMR significantly represses the cell growth and migration of NSCLC. We also found that the HOXB7/TMPO-AS1/Let-7b-5p axis mediated high expression of HMMR in NSCLC, depletion of TMPO-AS1 and over-expression the Let-7b-5p would result in decreased the expression of HMMR in NSCLC cells, the TMPO-AS1 was positively with the HMMR and negatively related to the Let-7b-5p in NSCLC. Overall, this study emphasized the significance of HOXB7/TMPO-AS1/Let-7b-5p axis mediated high expression of HMMR in cancer progression and Immune infiltration of LUAD.Conclusions: we demonstrated HMMR was elevated in LUAD and positively relation to poor prognosis. We find the hypoxia microenvironment and DNA hypomethylation able to up-regulation of the HMMR expression. Additionally, HMMR expression was positive with the diverse immune cell and immune regulator related gene in LUAD. Finally, we found that depletion of HMMR was inhibits the cell proliferation and migration ability of NSCLC cells. These findings suggest that HMMR could be served as a biomarker for prognosis and immune infiltration in LUAD.

scholarly journals Long Noncoding RNA GATA3-AS1 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Suppression of PTEN, CDKN1A, and TP53

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xuee Luo ◽  
Ning Zhou ◽  
Le Wang ◽  
Qinghua Zeng ◽  
Hongying Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cell Counting ◽  
Cell Growth And Migration ◽  
Expression Levels ◽  
Normal Tissues ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Cell Proliferation And Metastasis

Background. Long noncoding RNAs (lncRNAs) have been known to play important roles in the progression of various types of human cancer. LncRNA GATA3 antisense RNA 1, GATA3-AS1, has been reported to be associated with T-cell development and differentiation. However, the expression pattern and function of GATA3-AS1 in hepatocellular carcinoma (HCC) remain unknown. Methods. Real-time quantitative PCR (RT-qPCR) assay was conducted to detect GATA3-AS1 expression levels in 80 cases of pairs HCC tissues and matched normal tissues. Chi-squared (χ2) test was used to analyze the correlation between GATA3-AS1 expression and clinicopathologic variables. Survival curves were plotted using the Kaplan–Meier method and were compared via the log-rank test. The cell counting kit-8 (CCK-8) and wound scratch assays were applied to detect the effect of GATA3-AS1 knockdown and overexpression on cell growth and migration of HCC. RT-qPCR was performed for the detection of the phosphatase and tensin homolog (PTEN), cyclin-dependent kinase inhibitor 1A (CDKN1A), and tumor protein p53 (TP53) expression in HCC cells after GATA3-AS1 knockdown and overexpression. Results. GATA3-AS1 was significantly upregulated in HCC tissues compared with matched normal tissues. The high expression of GATA3-AS1 was significantly correlated with larger tumor size, advanced TNM stage, and more lymph node metastasis. High GATA3-AS1 expression was markedly correlated with shorter overall survival times of HCC patients. Furthermore, knockdown of GATA3-AS1 obviously inhibited Hep3B and HCCLM3 cell growth and migration, whereas overexpression of GATA3-AS1 had the opposite effects. In addition, GATA3-AS1 knockdown resulted in upregulated expression levels of tumor-suppressive genes, PTEN, CDKN1A, and TP53, in Hep3B and HCCLM3 cells, while restoration of GATA3-AS1 decreased PTEN, CDKN1A, and TP53 expression levels. Conclusion. Our data suggested that GATA3-AS1 promotes cell proliferation and metastasis of HCC by suppression of PTEN, CDKN1A, and TP53.

scholarly journals Hypoxia-induced HMMR Promotes Cell Proliferation, Migration and Immune Infiltrates in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Duan Lin can ◽  
Jiang Xiu lin ◽  
Tan Lin ◽  
Yuan Yi xiao ◽  
Wang Juan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Related Gene ◽  
Cell Growth And Migration ◽  
Immune Infiltration ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract BackgroundHyaluronan mediated motility receptor (also known as RHAMM) is another one of few defined hyaluronan receptors, play pivotal roles in cell growth. However, the relationships between HMMR and prognosis and tumor-infiltrating lymphocytes in lung adenocarcinoma remain unclear.MethodsHMMR expression was analyzed emoloyed the TIMER, GEPIA, UALCAN, CCLE databases, the prognosis of HMMR was analysis by prognoscan, KMplot and GEPIA databases. The GO and KEGG pathway was analysis by the DAVID and GSEA software. The correlation between the HMMR expression was analysis by the TIMER databases, the gene and protein networks was analysis by Genemania and STRING databases, the DNA methylation was analysis by the MethSurv and UALCAN databases, the gene mutation of HMMR was analysis by the cBioportal and COSMIC databases. The expression of HMMR was analysis by IHC and qPCR, the function of HMMR on cell proliferation and migration was examine by the cell growth curve, clone information, transwell and wound healing assay.ResultsIn this study, we find that HMMR was elevated in LUAD and it’s highly expression associated with the poor prognosis and lymph node metastasis. Furthermore, the expression of HMMR was induced by hypoxia in LUAD. HMMR expression level not only positively correlation with the different immune cells, but also positively correlation with the expression of immune checkpoints related gene, for instance, CD279, CD274, CTLA4, LAG3, PDCD1LG2, TIGIT and HAVCR2. Finally, depletion of HMMR significantly represses the cell growth and migration of NSCLC. Overall, this study emphasized the significance of HMMR in cancer progression and Immune infiltration of LUAD.ConclusionsWe demonstrated HMMR was elevated in LUAD and positively relation to poor prognosis. We find the hypoxia microenvironment and DNA hypomethylation able to up-regulation of the HMMR expression. Additionally, HMMR expression was positive with the diverse immune cell and immune regulator related gene in LUAD. Finally, we found that depletion of HMMR was inhibits the cell proliferation and migration ability of NSCLC cells. These findings suggest that HMMR could be served as a biomarker for prognosis and immune infiltration in LUAD.

Tenascin C to regulate the function of sHER3, an endogenous inhibitor of neuregulin signaling.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23002-e23002
Author(s):  
Chunlin Cai ◽  
Mojun Zhu ◽  
Nita J. Maihle
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Growth ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Cell Growth And Migration ◽  
Knock Out ◽  
Tenascin C ◽  
And Migration

e23002 Background: HER3 expression is associated with poor prognosis in melanoma patients but the mechanistic basis has not been determined. An endogenous secreted isoform of HER3, p85-sHER3, has been shown by us to inhibit neuregulin-1 mediated, Akt-dependent breast and ovarian cancer cell growth in vitro. Here we demonstrate that p85-sHER3 also regulates neuregulin-dependent melanoma cell migration via an Akt- independent, tenascin C-dependent mechanism. Methods: Immunoblot analysis and RT-PCR were used to study HER3 and p85-sHER expression. Cell proliferation and chamber assays were conducted to determine the effect of p85-sHER3 on melanoma cell growth and migration. Mass spectrometry (MS) was performed to identify sHER3-interacting proteins. CRSPR in vitro editing methods were used to knock out tenascin C (TNC) expression. Results: HER3 and p85-sHER3 were expressed in 5 of 6 human melanoma-derived cell lines tested, with exception of SK-MEL-103 which did not express either gene product. Exogenous addition of 10 nM p85-sHER3 inhibited growth in 3 cells lines, although Akt phosphorylation was not reduced. Protein extracts from M14-MEL cell conditioned media were characterized by MS, and identified p85-sHER3 and TNC. Their association was confirmed by co-immunoprecipitation. sHER3 was further shown to inhibit neuregulin stimulated cell migration in 2 cell lines which exhibited high levels of TNC. CRSPR knockout of TNC in these cell lines (but not in control lines) eliminated sHER3 inhibition of neuregulin stimulated melanoma cell migration. Conclusions: Our results suggest that p85-sHER3, predominantly secreted by HER3-expressing melanoma cells, inhibits melanoma cell proliferation and migration via an Akt-independent mechanism, which is likely achieved through interaction(s) with TNC. TNC promotes an intermediate adhesive state favoring cell migration and this state appears to be mediated by Rho-associated kinase signaling. The Rho inhibitor, CCG-203971 has been shown to inhibit melanoma cell migration. Together, these results suggest the existence of a TNC and HER3-dependent signaling pathway in melanoma that regulates cell migration, and therefore may be correlated with poor patient survival.

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

scholarly journals MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Zhenzhao Luo ◽  
Yue Fan ◽  
Xianchang Liu ◽  
Shuiyi Liu ◽  
Xiaoyu Kong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Growth ◽  
Suppressive Effect ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
And Migration ◽  
Cancer Tissues ◽  
Suppress Cell Proliferation

Background: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown. Methods: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells. Results: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3′UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration. Conclusions: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.

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