scholarly journals Hyaluromycin, a Novel Hyaluronidase Inhibitor, Attenuates Pancreatic Cancer Cell Migration and Proliferation

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Shiro Kohi ◽  
Norihiro Sato ◽  
Atsuhiro Koga ◽  
Keiji Hirata ◽  
Enjuro Harunari ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Critical Role ◽  
Ductal Adenocarcinoma ◽  
Antitumor Effects ◽  
Ribosomal Protein S6 ◽  
Hyaluronidase Inhibitor ◽  
Culture Extract ◽  
And Migration ◽  
Cell Migration And Proliferation ◽  
Proliferation And Migration

Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated production and degradation of hyaluronan (HA), a major component of extracellular matrix involved in the malignant phenotype of cancer. In particular, increased hyaluronidase (HYAL) activity plays a critical role in cancer progression, at least in part, by producing low-molecular-weight- (LMW-) HA or small fragments of HA, suggesting HYAL as a target for cancer treatment. Hyaluromycin, a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derivedStreptomyces hyaluromycinias a HYAL inhibitor. We investigated the antitumor effects of hyaluromycin in PDAC cells. We examined the effects of hyaluromycin on the proliferation and migration of PDAC cells. To elucidate the mechanisms underlying the effect of hyaluromycin on PDAC cells, we examined the concentration of LMW-HA in the conditioned media after treating PDAC cells with hyaluromycin. We demonstrate that hyaluromycin inhibits proliferation and migration of PDAC cells. We also found that these antitumor effects of hyaluromycin were associated with a decreased concentration of LMW-HA and a decreased phosphorylation of ribosomal protein S6. Our results suggest that hyaluromycin is a promising new drug against this highly aggressive neoplasm.

scholarly journals IncRNA MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cell lines by targeting miR-519e-5p/YWHAH

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Yan Zhou ◽  
Shanshan Liu ◽  
Yan Luo ◽  
Meiying Zhang ◽  
Xueling Jiang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Critical Role ◽  
Endocrine System ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
And Migration ◽  
Thyroid Cancer Cells ◽  
Proliferation And Migration

Thyroid cancer is a common malignant tumour of the endocrine system and ranks ninth in cancer incidence worldwide. An extensive body of evidence has demonstrated that lncRNAs play a critical role in the progression of thyroid cancer. The lncRNA MAPKAPK5-AS1 has been reported to be abnormally expressed and to play a role in the development of various human cancers. However, MAPKAPK5-AS1’s potential role in thyroid cancer progression remains unknown. The objective of our study was to explore the role and mechanism of MAPKAPK5-AS1 in thyroid cancer cells and provide a potential target for its biological diagnosis and treatment. We transfected sh-MAPKAPK5-AS1 and sh-NC into BCPAP and TPC-1 cells for loss-of-function assays. Results of RT-qPCR analysis demonstrated that MAPKAPK5-AS1 was more highly expressed in thyroid cancer cells compared to normal cells. Functional assays demonstrated that interfering with the expression of MAPKAPK5-AS1 notably repressed proliferation and invasion and accelerated apoptosis of BCPAP and TPC-1 cells. Mechanistically, we found that miR-519e-5p was negatively regulated by MAPKAPK5-AS1 and that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) was a target of miR-519e-5p. Additionally, rescue assays demonstrated that downregulation of MAPKAPK5-AS1 expression inhibited cell proliferation, migration, and invasion and promoted apoptosis by sponging miR-519e-5p, thereby increasing YWHAH expression. Ultimately, our study revealed that MAPKAPK5-AS1 promotes proliferation and migration of thyroid cancer cells by targeting the miR-519e-5p/YWHAH axis, which provides novel insight into the development and progression of thyroid cancer.

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Direct Target ◽  
And Migration ◽  
High Level ◽  
Cxcr5 Expression ◽  
Proliferation And Migration

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

scholarly journals NR5A2 transcriptional activation by BRD4 promotes pancreatic cancer progression by upregulating GDF15

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Feng Guo ◽  
Yingke Zhou ◽  
Hui Guo ◽  
Dianyun Ren ◽  
Xin Jin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Transcriptional Activation ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells ◽  
Gene Sets ◽  
And Migration

AbstractNR5A2 is a transcription factor regulating the expression of various oncogenes. However, the role of NR5A2 and the specific regulatory mechanism of NR5A2 in pancreatic ductal adenocarcinoma (PDAC) are not thoroughly studied. In our study, Western blotting, real-time PCR, and immunohistochemistry were conducted to assess the expression levels of different molecules. Wound-healing, MTS, colony formation, and transwell assays were employed to evaluate the malignant potential of pancreatic cancer cells. We demonstrated that NR5A2 acted as a negative prognostic biomarker in PDAC. NR5A2 silencing inhibited the proliferation and migration abilities of pancreatic cancer cells in vitro and in vivo. While NR5A2 overexpression markedly promoted both events in vitro. We further identified that NR5A2 was transcriptionally upregulated by BRD4 in pancreatic cancer cells and this was confirmed by Chromatin immunoprecipitation (ChIP) and ChIP-qPCR. Besides, transcriptome RNA sequencing (RNA-Seq) was performed to explore the cancer-promoting effects of NR5A2, we found that GDF15 is a component of multiple down-regulated tumor-promoting gene sets after NR5A2 was silenced. Next, we showed that NR5A2 enhanced the malignancy of pancreatic cancer cells by inducing the transcription of GDF15. Collectively, our findings suggest that NR5A2 expression is induced by BRD4. In turn, NR5A2 activates the transcription of GDF15, promoting pancreatic cancer progression. Therefore, NR5A2 and GDF15 could be promising therapeutic targets in pancreatic cancer.

scholarly journals hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

2021 ◽  
Vol 9 ◽  
Author(s):  
Chunli Gong ◽  
Huan Yang ◽  
Sumin Wang ◽  
Jiao Liu ◽  
Zhibin Li ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Promoter Activity ◽  
Related Factor ◽  
Human Telomerase Reverse Transcriptase ◽  
Protein Levels ◽  
Cellular Reactive Oxygen Species ◽  
And Migration ◽  
Human Telomerase ◽  
Nrf2 Expression ◽  
Proliferation And Migration

High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular reactive oxygen species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2-related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Here, we showed that hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. We further found that hTERT increases NRF2 expression at both the mRNA and protein levels. Our data also revealed that hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability. Using DNA pull-down/MS analysis, we found that hTERT can recruit YBX1 to upregulate NRF2 promoter activity. We also found that hTERT/YBX1 may localize to the P2 region of the NRF2 promoter. Taken together, our results demonstrate that hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter. These results provide a new theoretical basis for CRC treatment.

scholarly journals miR-183-5p promotes proliferation and migration in hepatocellular carcinoma by targeting IRS1 and its association with patient survival

2020 ◽  
Vol 35 (3) ◽  
pp. 83-89
Author(s):  
Rong Yan ◽  
Kang Li ◽  
Dawei Yuan ◽  
Haonan Wang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Progression ◽  
Normal Tissues ◽  
Report Analysis ◽  
In Vitro Effects ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Background: MiR-183-5p plays an important role in the pathophysiology of many tumors, while the role of MiR-183-5p in liver cancer is unclear. Methods: In this study, quantitative reverse transcription-polymerase chain reaction and Western blotting were used to detect the expression of miR-183-5p in liver cancer cell lines, liver cancer tissues, and normal tissues adjacent to the cancer, and to explore the mechanism of miR-183-5p regulating liver cancer progression. The in vitro effects of miR-183-5p were evaluated by CCK-8, colony formation test, and wound healing test. Various databases were used to predict the target mRNA of miR-183-5p and verified by luciferase report analysis. In addition, the effects of miR-183-5p and its target gene on the survival of patients with liver cancer were also analyzed. Results: miR-183-5p was highly expressed in hepatocellular carcinoma cells and tissues, and was related to some clinicopathological features. MiR-183-5p can promote the proliferation and migration of liver cancer cells. Using the bioinformatics database, we proved that miR-183-5p is related to the survival of liver cancer patients. Insulin receptor substrate 1 (IRS1) is a target of miR-183-5p, and luciferase analysis confirmed that miR-183-5p combines with the 3′-untranslated region (3′-UTR) of IRS1. Conclusion: The miR-183-5p/IRS1 axis may be a new target for liver cancer research.

scholarly journals MicroRNA-224 Promotes Pancreatic Cancer Cell Proliferation and Migration by Targeting the TXNIP-Mediated HIF1α Pathway

2018 ◽  
Vol 48 (4) ◽  
pp. 1735-1746 ◽  
Author(s):  
Guanghui Zhu ◽  
Lianming Zhou ◽  
Haijun Liu ◽  
Yuanzhou Shan ◽  
Xueli Zhang
Keyword(s):  
Cell Proliferation ◽  
Nuclear Export ◽  
Xenograft Model ◽  
Ductal Adenocarcinoma ◽  
Luciferase Reporter ◽  
Mouse Xenograft Model ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: MicroRNAs (miRNAs) have been shown to participate in the development of pancreatic ductal adenocarcinoma (PDAC) by modulating multiple cellular processes. Increased miR-224 expression enhances proliferation and metastasis in human cancers. This study aimed to investigate the role of miR-224 and its underlying mechanism of action in PDAC. Methods: BrdU, MTT, and cell migration assays were performed to determine cell proliferation, viability, and migration, respectively. The binding sites of miR-224 were identified using a luciferase reporter system, whereas protein expression of target genes was determined by immunoblotting and immunofluorescence analyses. A BALB/c nude mouse xenograft model was used to evaluate the role of miR-224 in vivo. Results: We demonstrated that miR-224 expression was enhanced in PDAC cells and tissues, and was related to migration and proliferation. Noticeably, miR-224 overexpression promoted the proliferation, migration, and metastasis of Panc1 cells, while miR-224 inhibition had the reverse effect on PDAC cells. Moreover, we found that thioredoxin-interacting protein (TXNIP) is a target of miR-224. The results also indicated that miR-224 inversely regulated TXNIP by binding directly to its 3′-untranslated region, which resulted in the activation of hypoxia-inducible factor 1α (HIF1α). Further, either TXNIP re-expression or HIF1α depletion abolished the effects of miR-224 on the proliferation and migration of PDAC cells in vitro and in vivo. Regarding the relationship of TXNIP and HIF1α, we found that TXNIP mediated the nuclear export of HIF1α and its degradation by forming a complex with HIF1α. Conclusion: The miR-224-TXNIP-HIF1α axis may be useful in developing novel therapies for PDAC.

scholarly journals LncRNA RNA Component of Mitochondrial RNA-Processing Endoribonuclease Promotes AKT-Dependent Breast Cancer Growth and Migration by Trapping MicroRNA-206

2021 ◽  
Vol 9 ◽  
Author(s):  
Yingdan Huang ◽  
Bangxiang Xie ◽  
Mingming Cao ◽  
Hua Lu ◽  
Xiaohua Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Rna Processing ◽  
Cancer Development ◽  
Mitochondrial Rna ◽  
Cancer Cell Growth ◽  
Cell Growth And Migration ◽  
Downstream Target ◽  
And Migration ◽  
Proliferation And Migration

The RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) was recently shown to play a role in cancer development. However, the function and mechanism of RMRP during cancer progression remain incompletely understood. Here, we report that RMRP is amplified and highly expressed in various malignant cancers, and the high level of RMRP is significantly associated with their poor prognosis, including breast cancer. Consistent with this, ectopic RMRP promotes proliferation and migration of TP53-mutated breast cancer cells, whereas depletion of RMRP leads to inhibition of their proliferation and migration. RNA-seq analysis reveals AKT as a downstream target of RMRP. Interestingly, RMRP indirectly elevates AKT expression by preventing AKT mRNA from miR-206-mediated targeting via a competitive sequestering mechanism. Remarkably, RMRP endorses breast cancer progression in an AKT-dependent fashion, as knockdown of AKT completely abolishes RMRP-induced cancer cell growth and migration. Altogether, our results unveil a novel role of the RMRP-miR-206-AKT axis in breast cancer development, providing a potential new target for developing an anti-breast cancer therapy.

scholarly journals TGFBI Protein Is Increased in the Urine of Patients with High-Grade Urothelial Carcinomas, and Promotes Cell Proliferation and Migration

2019 ◽  
Vol 20 (18) ◽  
pp. 4483 ◽  
Author(s):  
Kerstin Lang ◽  
Selcan Kahveci ◽  
Nadine Bonberg ◽  
Katharina Wichert ◽  
Thomas Behrens ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
De Novo ◽  
Smoking Status ◽  
Critical Role ◽  
High Grade ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Muscle Invasive ◽  
Population Controls ◽  
Proliferation And Migration

Here, we discovered TGFBI as a new urinary biomarker for muscle invasive and high-grade urothelial carcinoma (UC). After biomarker identification using antibody arrays, results were verified in urine samples from a study population consisting of 303 patients with UC, and 128 urological and 58 population controls. The analyses of possible modifying factors (age, sex, smoking status, urinary leukocytes and erythrocytes, and history of UC) were calculated by multiple logistic regression. Additionally, we performed knockdown experiments with TGFBI siRNA in bladder cancer cells and investigated the effects on proliferation and migration by wound closure assays and BrdU cell cycle analysis. TGFBI concentrations in urine are generally increased in patients with UC when compared to urological and population controls (1321.0 versus 701.3 and 475.6 pg/mg creatinine, respectively). However, significantly increased TGFBI was predominantly found in muscle invasive (14,411.7 pg/mg creatinine), high-grade (8190.7 pg/mg) and de novo UC (1856.7 pg/mg; all p < 0.0001). Knockdown experiments in vitro led to a significant decline of cell proliferation and migration. In summary, our results suggest a critical role of TGFBI in UC tumorigenesis and particularly in high-risk UC patients with poor prognosis and an elevated risk of progression on the molecular level.

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