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

2021 ◽  
Author(s):  
Chunli Gong ◽  
Huan Yang ◽  
Sumin Wang ◽  
Jiao Liu ◽  
Zhibin Li ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Promoter Activity ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Related Factor ◽  
Human Telomerase Reverse Transcriptase ◽  
Protein Levels ◽  
And Migration ◽  
Nrf2 Expression ◽  
Proliferation And Migration

Abstract Background: 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. Herein, we sought to determine the relationship of hTERT and NRF2 in the progression of CRC and to elucidate the underlying molecular mechanisms.Methods: qPCR, Western blot, Immunohistochemistry, immunofluorescence assays were used to detect the mRNA and protein expression of hTERT, NRF2 and YBX1 in CRC cell lines and tissues.CCK8 and colony formation were used to detect the proliferation of CRC cells, transwell assay was used to detect the migration of CRC cells. Dual-luciferase reporter assays were used to detect the promoter activity of NRF2. DNA pull-down/MS analysis was used to identify NRF2 promoter binding proteins. ChIP-qPCR was used to detect the YBX1binding sequences of NRF2 promoter.Results: Both hTERT and NRF2 are highly expressed in CRC tissues and associated with poor diagnosis. hTERT increases NRF2 expression at both the mRNA and protein levels. hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. Moreover, hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability, and hTERT recruits YBX1 to upregulate NRF2 promoter activity thus increases NRF2 expression and enhances CRC proliferation and migration.Conclusions: hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter.

scholarly journals Cardiac fibroblasts require focal adhesion kinase for normal proliferation and migration

2009 ◽  
Vol 296 (3) ◽  
pp. H627-H638 ◽  
Author(s):  
Ana Maria Manso ◽  
Seok-Min Kang ◽  
Sergey V. Plotnikov ◽  
Ingo Thievessen ◽  
Jaewon Oh ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Adult Mouse ◽  
Cardiac Fibroblasts ◽  
Focal Adhesions ◽  
Protein Levels ◽  
Tyrosine Kinase 2 ◽  
A Cell ◽  
And Migration ◽  
Proliferation And Migration

Migration and proliferation of cardiac fibroblasts (CFs) play an important role in the myocardial remodeling process. While many factors have been identified that regulate CF growth and migration, less is known about the signaling mechanisms involved in these processes. Here, we utilized Cre-LoxP technology to obtain focal adhesion kinase (FAK)-deficient adult mouse CFs and studied how FAK functioned in modulating cell adhesion, proliferation, and migration of these cells. Treatment of FAKflox/flox CFs with Ad/Cre virus caused over 70% reduction of FAK protein levels within a cell population. FAK-deficient CFs showed no changes in focal adhesions, cell morphology, or protein expression levels of vinculin, talin, or paxillin; proline-rich tyrosine kinase 2 (Pyk2) expression and activity were increased. Knockdown of FAK protein in CFs increased PDGF-BB-induced proliferation, while it reduced PDGF-BB-induced migration. Adhesion to fibronectin was not altered. To distinguish between the function of FAK and Pyk2, FAK function was inhibited via adenoviral-mediated overexpression of the natural FAK inhibitor FAK-related nonkinase (FRNK). Ad/FRNK had no effect on Pyk2 expression, inhibited the PDGF-BB-induced migration, but did not change the PDGF-BB-induced proliferation. FAK deficiency had only modest effects on increasing PDGF-BB activation of p38 and JNK MAPKs, with no alteration in the ERK response vs. control cells. These results demonstrate that FAK is required for the PDGF-BB-induced migratory response of adult mouse CFs and suggest that FAK could play an essential role in the wound-healing response that occurs in numerous cardiac pathologies.

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 Na+/Ca2+ exchangers regulate the migration and proliferation of human gastric myofibroblasts

2013 ◽  
Vol 305 (8) ◽  
pp. G552-G563 ◽  
Author(s):  
Lajos V. Kemény ◽  
Andrea Schnúr ◽  
Mátyás Czepán ◽  
Zoltán Rakonczay ◽  
Eleonóra Gál ◽  
...  
Keyword(s):  
Tumor Development ◽  
Oscillatory Activity ◽  
Pcr Analysis ◽  
Gastric Diseases ◽  
Protein Levels ◽  
Intracellular Ca ◽  
Transitional Cells ◽  
And Migration ◽  
Proliferation And Migration

Gastrointestinal myofibroblasts are contractile, electrically nonexcitable, transitional cells that play a role in extracellular matrix production, in ulcer healing, and in pathophysiological conditions they contribute to chronic inflammation and tumor development. Na+/Ca2+ exchangers (NCX) are known to have a crucial role in Ca2+ homeostasis of contractile cells, however, no information is available concerning the role of NCX in the proliferation and migration of gastrointestinal myofibroblasts. In this study, our aim was to investigate the role of NCX in the Ca2+ homeostasis, migration, and proliferation of human gastrointestinal myofibroblasts, focusing on human gastric myofibroblasts (HGMs). We used microfluorometric measurements to investigate the intracellular Ca2+ and Na+ concentrations, PCR analysis and immunostaining to show the presence of the NCX, patch clamp for measuring NCX activity, and proliferation and migration assays to investigate the functional role of the exchanger. We showed that 53.0 ± 8.1% of the HGMs present Ca2+ oscillations, which depend on extracellular Ca2+ and Na+, and can be inhibited by NCX inhibitors. NCX1, NCX2, and NCX3 were expressed at both mRNA and protein levels in HGMs, and they contribute to the intracellular Ca2+ and Na+ homeostasis as well, regardless of the oscillatory activity. NCX inhibitors significantly blocked the basal and insulin-like growth factor II-stimulated migration and proliferation rates of HGMs. In conclusion, we showed that NCX plays a pivotal role in regulating the Ca2+ homeostasis, migration, and proliferation of HGMs. The inhibition of NCX activity may be a potential therapeutic target in hyperproliferative gastric diseases.

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 The Association of Aberrant Expression of FGF1 and mTOR-S6K1 in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Tinghui Duan ◽  
Diyuan Zhou ◽  
Yizhou Yao ◽  
Xinyu Shao
Keyword(s):  
Colorectal Cancer ◽  
Malignant Neoplasms ◽  
Aberrant Expression ◽  
Protein Levels ◽  
And Migration ◽  
High Level ◽  
Proliferation And Migration

Colorectal cancer (CRC) is one of the most frequent malignant neoplasms worldwide, and the effect of treatments is limited. Fibroblast growth factor 1 (FGF1) has been involved in a wide variety of several malignant diseases and takes part in the tumorigenesis of CRC. However, the function and mechanism of FGF1 in CRC remains elusive. In this study, the results indicated that FGF1 is elevated in CRC tissues and linked with poor prognosis (P < 0.001). In subgroup analysis of FGF1 in CRC, regardless of any clinic-factors except gender, high level FGF1 expression was associated with markedly shorter survival (P < 0.05). In addition, the expression of p-S6K1 and FGF1 was not associated in normal tissue (P = 0.781), but their expression was closely related in tumor tissue (P = 0.010). The oncogenic role of FGF1 was determined using in vitro and in vivo functional assays. FGF1 depletion inhibited the proliferation and migration of CRC cells in vitro and vivo. FGF1 was also significantly correlated with mTOR-S6K1 pathway on the gene and protein levels (P < 0.05). In conclusion, FGF1 acts as a tumor activator in CRC, and against FGF1 may provide a new visual field on treating CRC, especially for mTORC1-targeted resistant patients.

scholarly journals Apolipoprotein M inhibits proliferation and migration of larynx carcinoma cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haixiang Xue ◽  
Miaomei Yu ◽  
Ying Zhou ◽  
Jun Zhang ◽  
Qinfeng Mu ◽  
...  
Keyword(s):  
Western Blot ◽  
Mrna Level ◽  
Carcinoma Cells ◽  
Mrna Levels ◽  
Apolipoprotein M ◽  
Protein Levels ◽  
Pcr Technology ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract Prior studies have shown that apolipoprotein M (APOM) is involved in the development of some cancers. Here we investigated the effects of APOM on larynx cancer (LC). 20 patients with vocal cord polyps and 18 patients with LC were included in this study. The protein and mRNA levels of the samples were analysed using the Wes-ProteinSimple system (or traditional Western blot) and PCR technology, respectively. APOM protein level in cancer tissues was lower than that in paracarcinomatous (P = 0.0003) and polyp tissues (P < 0.0001). APOM overexpression significantly inhibited TU686 cell proliferation (P < 0.0001) and migration (P < 0.01), and increased expression of vitamin D receptor (VDR, P < 0.0001) as well as nuclear factor erythroid 2-like 3 (NFE2L3, P = 0.0215). In addition, matrix metalloproteinase-10 (MMP-10) mRNA level was significantly reduced in the APOM overexpression group (P = 0.0077). However, Western blot analysis showed that APOM overexpression did not change VDR, NFE2L3 and MMP-10 protein levels (P > 0.05). In summary, APOM inhibits the proliferation and migration of LC cells, but may not be related to VDR, NFE2L3 and MMP-10, which needs further study.

scholarly journals MiR-629-5p promotes colorectal cancer progression through targetting CXXC finger protein 4

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Jinlai Lu ◽  
Shuirong Lu ◽  
Jingze Li ◽  
Qi Yu ◽  
Lang Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
Tumor Promoter ◽  
Finger Protein ◽  
Cell Proliferation And Migration ◽  
Colorectal Cancer Progression ◽  
And Migration ◽  
Proliferation And Migration

MiR-629-5p has been shown to function as a tumor promoter in some types of cancer. However, the role of miR-629-5p in colorectal cancer remains unclear. Here, the significant up-regulation of miR-629-5p in colorectal cancer tissues and cell lines was observed. Overexpression of miR-629-5p showed a positive effect on cell proliferation and migration. The enhanced miR-629-5p level also suppressed cell apoptosis and resulted in a low Bax level and a high Bcl-2 level. Further down-regulating miR-629-5p demonstrated opposite effects. CXXC finger protein 4 (CXXC4) was predicted as a direct target of miR-629-5p. Dual-luciferase reporter and Western blotting assays exhibited miR-629-5p directly bound to the 3′UTR of CXXC4 and then down-regulated its expression at post-transcriptional level. CXXC4 knockdown rescued the decreased cell proliferation and migration and the enhanced cell apoptosis induced by inhibiting miR-629-5p expression. Notably, overexpression of miR-629-5p also conferred 5-fluorouracil sensitivity, which was partly abrogated by coexpression of CXXC4. Overall, the results presented here suggest that miR-629-5p functions as a tumor promoter by improving proliferation and migration and repressing apoptosis and 5-FU sensitivity in colorectal cancer progression by directly down-regulating CXXC4.

scholarly journals Cell confluence regulates claudin-2 expression: possible role for ZO-1 and Rac

2018 ◽  
Vol 314 (3) ◽  
pp. C366-C378 ◽  
Author(s):  
Yasaman Amoozadeh ◽  
Shaista Anwer ◽  
Qinghong Dan ◽  
Shruthi Venugopal ◽  
Yixuan Shi ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Epithelial Mesenchymal Transition ◽  
Feedback Mechanism ◽  
Small Gtpase ◽  
Immunofluorescent Staining ◽  
Mesenchymal Transition ◽  
P21 Activated Kinase ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Proliferation And Migration

Claudin-2 (Cldn-2) is a channel-forming tight junction (TJ) protein in the proximal tubules that mediates paracellular Na+ transport and has also emerged as a regulator of proliferation and migration. Expression of Cldn-2 is altered by numerous stimuli, but the underlying mechanisms remain incompletely understood. Here we show that Cldn-2 protein and mRNA expression were low in subconfluent tubular cells and increased during junction maturation. Cldn-1 or occludin did not exhibit similar confluence-dependence. Conversely, disruption of TJs by Ca2+ removal or silencing of zonula occludens-1 (ZO-1) or ZO-2 induced a large drop in Cldn-2 abundance. Immunofluorescent staining revealed a more uneven Cldn-2 staining in nascent, Cldn-1-positive TJs. Subconfluence and ZO-1 silencing augmented Cldn-2 degradation and reduced Cldn-2 promoter activity, suggesting that insertion into the TJs slows Cldn-2 turnover. Indeed, blocking endocytosis or lysosomal degradation increased Cldn-2 abundance. Cell confluence increased expression of the junctional adapters ZO-1 and -2, and the small GTPase Rac, and elevated Rac activity and p21-activated kinase (Pak) phosphorylation, suggesting that they might mediate confluence-dependent Cldn-2 regulation. Indeed, Rac silencing or Pak inhibition strongly reduced Cldn-2 protein abundance, which was likely the combined effect on turnover, as these interventions reduced Cldn-2 promoter activity and augmented Cldn-2 degradation. Taken together, our data suggest that TJ integrity and maturity, ZO-1 expression/TJ localization, and Rac/Pak control Cldn-2 degradation and synthesis. A feedback mechanism connecting Cldn-2 expression with junction remodeling, e.g., during wound healing, epithelial-mesenchymal transition, or tumor metastasis formation, may have important downstream effects on permeability, proliferation, and migration.

Sign in / Sign up

Export Citation Format

Share Document