Phosphatase of regenerating liver maintains cellular magnesium homeostasis

2018 ◽  
Vol 475 (6) ◽  
pp. 1129-1139 ◽  
Author(s):  
Atsushi Yoshida ◽  
Yosuke Funato ◽  
Hiroaki Miki
Keyword(s):  
Cancer Progression ◽  
Functional Relationship ◽  
Cultured Cells ◽  
Culture Conditions ◽  
Signal Transducer ◽  
Regenerating Liver ◽  
Mrna Transcription ◽  
Protein Levels ◽  
Magnesium Homeostasis ◽  
Phosphatase Of Regenerating Liver

Phosphatase of regenerating liver (PRL) is highly expressed in malignant cancers and promotes cancer progression. Recent studies have suggested its functional relationship with Mg2+, but the importance and molecular details of this relationship remain unknown. Here, we report that PRL expression is regulated by Mg2+ and PRL protects cells from apoptosis under Mg2+-depleted conditions. When cultured cells were subjected to Mg2+ depletion, endogenous PRL protein levels increased significantly. siRNA-mediated knockdown of endogenous PRL did not significantly affect cell proliferation under normal culture conditions, but it increased cell death after Mg2+ depletion. Imaging analyses with a fluorescent probe for Mg2+ showed that PRL knockdown severely reduced intracellular Mg2+ levels, indicating a role for PRL in maintaining intracellular Mg2+. We also examined the mechanism of augmented expression of PRL proteins and found that PRL mRNA transcription was stimulated by Mg2+ depletion. A series of analyses revealed the activation and the crucial importance of signal transducer and activator of transcription 1 in this process. Collectively, these results implicate PRL in maintaining cellular Mg2+ homeostasis.

scholarly journals Magnesium-sensitive upstream ORF controls PRL phosphatase expression to mediate energy metabolism

2019 ◽  
Vol 116 (8) ◽  
pp. 2925-2934 ◽  
Author(s):  
Serge Hardy ◽  
Elie Kostantin ◽  
Shan Jin Wang ◽  
Tzvetena Hristova ◽  
Gabriela Galicia-Vázquez ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Rapid Change ◽  
Metabolic Reprogramming ◽  
Regenerating Liver ◽  
Energy Status ◽  
Intracellular Magnesium ◽  
Cellular Energy ◽  
Magnesium Homeostasis ◽  
Upstream Orf ◽  
Cellular Bioenergetics

Phosphatases of regenerating liver (PRL-1, PRL-2, and PRL-3, also known as PTP4A1, PTP4A2, and PTP4A3) control magnesium homeostasis through an association with the CNNM magnesium transport regulators. Although high PRL levels have been linked to cancer progression, regulation of their expression is poorly understood. Here we show that modulating intracellular magnesium levels correlates with a rapid change of PRL expression by a mechanism involving its 5′UTR mRNA region. Mutations or CRISPR-Cas9 targeting of the conserved upstream ORF present in the mRNA leader derepress PRL protein synthesis and attenuate the translational response to magnesium levels. Mechanistically, magnesium depletion reduces intracellular ATP but up-regulates PRL protein expression via activation of the AMPK/mTORC2 pathway, which controls cellular energy status. Hence, altered PRL-2 expression leads to metabolic reprogramming of the cells. These findings uncover a magnesium-sensitive mechanism controlling PRL expression, which plays a role in cellular bioenergetics.

scholarly journals Regulatory mechanisms of phosphatase of regenerating liver (PRL)-3

2016 ◽  
Vol 44 (5) ◽  
pp. 1305-1312 ◽  
Author(s):  
Teresa Rubio ◽  
Maja Köhn
Keyword(s):  
Drug Development ◽  
Posttranslational Modifications ◽  
Human Cancer ◽  
Regulatory Mechanisms ◽  
Therapeutic Drug ◽  
Regenerating Liver ◽  
Cancer Types ◽  
Tumor Metastases ◽  
Phosphatase Of Regenerating Liver ◽  
Incomplete Picture

The phosphatase of regenerating liver (PRL)-3 is overexpressed in many human cancer types and tumor metastases when compared with healthy tissues. Different pathways and mechanisms have been suggested to modulate PRL-3 expression levels and activity, giving some valuable insights but still leaving an incomplete picture. Investigating these mechanisms could provide new targets for therapeutic drug development. Here, we present an updated overview and summarize recent findings concerning the different PRL-3 expression regulatory mechanisms and posttranslational modifications suggested to modulate the activity, localization, or stability of this phosphatase.

scholarly journals Phosphatase of regenerating liver-3 (PRL-3) is overexpressed in classical Hodgkin lymphoma and promotes survival and migration

2018 ◽  
Vol 7 (1) ◽  
Author(s):  
Magnus Aassved Hjort ◽  
Håkon Hov ◽  
Pegah Abdollahi ◽  
Esten Nymoen Vandsemb ◽  
Unn-Merete Fagerli ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Regenerating Liver ◽  
Classical Hodgkin Lymphoma ◽  
And Migration ◽  
Phosphatase Of Regenerating Liver

scholarly journals Overexpression of IRS-4 Correlates with Procaspase 3 Levels in Tumoural Tissue of Patients with Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-14
Author(s):  
Patricia Sanmartín-Salinas ◽  
Luis G. Guijarro
Keyword(s):  
Colorectal Cancer ◽  
Caspase 3 ◽  
Cultured Cells ◽  
Cyclin Dependent Kinase ◽  
Kinase Activation ◽  
Tnm System ◽  
Protein Levels ◽  
Receptor Signalling ◽  
T Values

We reported that insulin receptor substrate 4 (IRS-4) levels increased in tissue from colorectal cancer (CRC) patients and promoted retinoblastoma-cyclin-dependent kinase activation. The aim of the present study was to evaluate the effect of IRS-4 on IGF-1 receptor pathway and its impact on procaspase 3 and PARP expression in RKO and HepG2 cancer cell lines. The results obtained in vitro were compared with those obtained from biopsies of patients with CRC (n = 18), tubulovillous adenomas (TA) (n = 2) and in matched adjacent normal colorectal (MANC) tissue (n = 20). IRS-4 overexpression in cultured cells induced the overactivation of IGF-1/BRK/AKT/GSK-3/β-catenin/cyclin D1 pathways, which led to increased expression of procaspase 3 and PARP protein levels. Studies carried out on CRC and TA tissues revealed the overactivation of the IGF-1 receptor signalling pathway, as well as the overexpression of procaspase 3 and PARP in tumoural tissue with respect to MANC tissue. The upregulation of IRS-4 in tumoural samples correlated significantly with the increase in pIGF-1 receptor (Tyr 1165/1166) (r = 0.84; p < 0.0001), procaspase 3 (r = 0. 77; p < 0. 0005) and PARP (r = 0. 89; p < 0. 0005). Similarly, we observed an increase in the proteolysis of procaspase 3 in tumoural tissue with respect to MANC tissue, which correlated significantly with the degradation of PARP (r = 0.86; p < 0.0001), p53 (r = 0.84; p < 0.0001), and GSK-3 (r = 0.78; p < 0.0001). The stratification of patient samples using the TNM system revealed that procaspase 3 and caspase 3 increased gradually with T values, which suggests their involvement in the size and local invasion of primary tumours. Taken together, our findings suggest that IRS-4 overexpression promotes the activation of the IGF-1 receptor pathway, which leads to the increase in procaspase 3 levels in CRC.

scholarly journals 34 LIFESPAN AND CHROMOSOMAL STABILITY OF BOVINE AND PORCINE FETAL FIBROBLAST CELLS CULTURED IN VITRO

2005 ◽  
Vol 17 (2) ◽  
pp. 167 ◽  
Author(s):  
A.M. Giraldo ◽  
J.W. Lynn ◽  
C.E. Pope ◽  
R.A. Godke ◽  
K.R. Bondioli
Keyword(s):  
Cell Lines ◽  
Cultured Cells ◽  
Culture Conditions ◽  
Cycle Duration ◽  
Fibroblast Cells ◽  
Proliferative Capacity ◽  
Chromosomal Stability ◽  
Fetal Fibroblasts ◽  
Fetal Bovine

The low efficiency of nuclear transfer (NT) has been related to factors such as mitochondria heteroplasmy, failure of genomic activation, and asynchrony between the donor karyoplast and recipient cytoplast. Few studies have characterized donor cell lines in terms of proliferative capacity and chromosomal stability. It is known that suboptimal culture conditions can induce chromosomal abnormalities, and the use of aneuploid donor cells during NT can lead to a high incidence of abnormal cloned embryos (Giraldo et al. 2004 Reprod. Fertil. Dev. 16, 124 abst). The purpose of this study was to determine the lifespan and chromosomal stability of bovine and porcine fetal cells. Four bovine and four porcine fibroblast cells lines were established from 50-day and 40-day fetuses, respectively. Cells were cultured in DMEM medium supplemented with 10% fetal bovine serum and 1% penicillin and streptomycin at 37°C in 5% CO2. Each cell line was passaged to senescence. Total population doublings (PDs) and cell cycle duration were calculated. To determine the chromosome numbers at different PDs, cells were synchronized in metaphase, fixed, and stained. ANOVA and chi-square tests were used to analyze differences in PDs and proportion of aneuploid cells between cell lines, respectively (P < 0.05). The results show that proliferative capacity was not different between cell lines derived from the same species. Cell lines derived from bovine and porcine fetuses had different in vitro lifespans (33 PDs vs. 42 PDs, respectively; P < 0.05). The mean length of the cell cycles for both bovine and porcine fetal fibroblasts was ∼28 h. The percentage of aneupliod cells in both bovine and porcine fetal cell lines increased progressively with duration of culture (see Table) and was high throughout the study. The proliferative capacity of cultured cells was similar within individuals of the same species, but growth characteristics differed between fetal bovine and porcine cell lines. The progressive increase of aneuploid cells could be due to suboptimal culture conditions or unusual chromosome instability in the particular fetuses used. These data demonstrate the importance of determining chromosome content and the use of cells at early passages to decrease the percentage of aneuploid reconstructed embryos and increase the efficiency of NT.

scholarly journals LINC00885 promotes cervical cancer progression through sponging miR-3150b-3p and upregulating BAZ2A

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Yeling Liu ◽  
Jingrui Chen ◽  
Lizhong Zhou ◽  
Chunhua Yin
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Animal Experiments ◽  
Cell Behaviors ◽  
Protein Levels ◽  
Non Coding Rna ◽  
Promising Therapeutic Target ◽  
Proliferation And Apoptosis ◽  
Non Coding Rnas ◽  
Oncogenic Function

Abstract Background Cervical cancer (CC) is one of the most common malignancies affecting female worldwide. Long non-coding RNAs (lncRNAs) are increasingly indicated as crucial participants and promising therapeutic targets in human cancers. The main objective of this study was to explore the functions and mechanism of LINC00885 in CC. Methods RT-qPCR and western blot were used to detect RNA and protein levels. Functional and mechanism assays were respectively done for the analysis of cell behaviors and molecular interplays. Results Long intergenic non-coding RNA 885 (LINC00885) was discovered to be upregulated in CC tissues and cell lines through bioinformatics analysis and RT-qPCR. Overexpression of LINC00885 promoted proliferation and inhibited apoptosis, whereas its silence exerted opposite effects. The cytoplasmic localization of LINC00885 was ascertained and furthermore, LINC00885 competitively bound with miR-3150b-3p to upregulate BAZ2A expression in CC cells. Rescue assays confirmed that LINC00885 regulated CC proliferation and apoptosis through miR-3150b-3p/BAZ2A axis. Finally, we confirmed that LINC00885 aggravated tumor growth through animal experiments. Conclusions LINC00885 exerted oncogenic function in CC via regulating miR-3150b-3p/BAZ2A axis. These findings suggested LINC00885 might serve as a potential promising therapeutic target for CC patients.

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 The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer

2019 ◽  
Author(s):  
Siyuan Cheng ◽  
Nestor Prieto-Dominguez ◽  
Shu Yang ◽  
Zachary M. Connelly ◽  
Samantha StPierre ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Hippo Pathway ◽  
Luciferase Reporter ◽  
Low Grade ◽  
Beta Catenin ◽  
High Grade ◽  
Protein Levels ◽  
Neuroendocrine Prostate Cancer ◽  
Functional Involvement

ABSTRACTBACKGROUNDAfter long-term androgen deprivation therapy, 25-30% prostate cancer (PCa) acquires an aggressive neuroendocrine (NE) phenotype. Dysregulation of YAP1, a key transcription coactivator of the Hippo pathway, has been related to cancer progression. However, its role in neuroendocrine prostate cancer (NEPC) has not been assessed.METHODSImmunohistochemistry was used to evaluate YAP1 protein levels during PCa initiation and progression. YAP1 knockdown and luciferase reporter assays were used to evaluate the ability of YAP1 to modulate Wnt/beta-Catenin signaling.RESULTSYAP1 expression was present in the basal epithelial cells in benign prostatic tissues, lost in low grade PCa, but elevated in high grade prostate adenocarcinomas. Interestingly, the expression of YAP1 was reduced/lost in both human and mouse NEPC. Finally, YAP1 knockdown in PCa cells activates Wnt/beta-Catenin signaling, which has been implicated in NE differentiation of PCa, supporting a functional involvement of the loss of YAP1 expression in NEPC development.CONCLUSIONSThe expression of YAP1 is elevated in high grade prostate adenocarcinomas while lost in NEPC. Reduced YAP1 activates Wnt/beta-Catenin signaling in PCa cells. These results suggest that when applied to PCa patients, YAP1 inhibitors shall be used with caution.

Sign in / Sign up

Export Citation Format

Share Document