Macrophages expedite cell proliferation of prostate intraepithelial neoplasia through their downstream target ERK

Cell proliferation, caspase 3 and pi-form of glutathione S transferase (GSTP1) were evaluated in prostate carcinoma (PCA), proliferative inflammatory atrophy (PIA) and prostate intraepithelial neoplasia (PIN). Forty biopsies were classified as: without morphological lesions (controls: CTR), PIA, PIN and PCA. Ki67, caspase3 and GSTP1 were immunostained. The following estimates were performed: Numerical densities of Ki67+ cells (NVEPKi67), of all epithelial cells (NVEPtotal) and of GSTP1+ cells (NVEPGSTP1); labelling index for Ki67 (LIKi67); volume fraction to caspase 3 positive tissue (VVcaspase 3) and of GSTP1 positive tissue (VVGSTP1). ANOVA was performed to compare the groups. NVEPtotal and NVEPKi67 were increased in PIA. LIKi67 was only increased in PCA. VVcaspase 3 was decreased in PIN and PCA. VVEGSTP1 was decreased in PCA. In our results PIA lacks the characteristics of a premalignant lesion. The result may be explained by the use of unbiased quantitative methods, the inadequate definition of PIA and the scarce inflammation observed in the samples with PIA included in this study.

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SAD-A Promotes Pancreatic ß-Cell Proliferation by Regulating ß-Cell Cycle as a Downstream Target of mTORC1 Signaling

Diabetes ◽

10.2337/db18-53-or ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 53-OR

Author(s):

JIA NIE ◽

NICOLAS MUSI ◽

YUGUANG SHI

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Downstream Target ◽

Mtorc1 Signaling

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LncRNA MAFG-AS1 regulates miR-125b-5p/SphK1 axis to promote the proliferation, migration, and invasion of bladder cancer cells

Human Cell ◽

10.1007/s13577-020-00470-3 ◽

2021 ◽

Author(s):

Chenye Tang ◽

Yuntao Wu ◽

Xiao Wang ◽

Kean Chen ◽

Zhiling Tang ◽

...

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Migration And Invasion ◽

Inhibitory Effects ◽

Potential Therapeutic Target ◽

Downstream Target ◽

Transwell Invasion Assay ◽

Tumor Tissues ◽

Bladder Cancer Cells ◽

Luciferase Activity Assay

AbstractMAFG-AS1 is an oncogenic lncRNA in multiple types of cancer. However, its role in bladder cancer (BC) remains unclear. The present study aimed to investigate the function of MAFG-AS1 in BC. BC and paired non-tumor tissues were collected. Two BC cell lines HT01197 and HT-1376 were used. Dual luciferase activity assay, RT-qPCR, western blot, CCK-8, transwell invasion assay, and wound healing assay were performed. We found that MAFG-AS1 was significantly up-regulated in BC tissues and predicted a poor survival rate. MAFG-AS1 interacted with miR-125b-5p. However, the expression levels of MAFG‑AS1 and miR-125b-5p were not obviously correlated in BC tissues, and MAFG‑AS1 and miR-125b-5p did not regulate the expression of each other. Interestingly, we found that SphK1, a downstream target of miR-125b-5p, was negatively correlated with miR-125b-5p, while it was positively correlated with MAFG-AS1 across BC tissues. In addition, overexpression of MAFG‑AS1 upregulated the expression of SphK1 in BC cells, and attenuated the inhibitory effects of miR-125b-5p on the expression of SphK1. Functional assays showed that overexpression of MAFG‑AS1 promoted BC cell proliferation, migration, and invasion, while its effects were attenuated by overexpression of miR-125b-5p. Moreover, overexpression of miR-125b-5p inhibited BC cell proliferation, migration, and invasion, while its effects were alleviated by overexpression of SphK1. Taken together, our findings demonstrated that MAFG-AS1 has an oncogenic role in BC by regulating the miR-125b-5p/SphK1 axis. MAFG-AS1 might serve as a good diagnostic marker and a potential therapeutic target of BC.

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DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

Cell Death and Disease ◽

10.1038/s41419-021-03796-4 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Yixin Tong ◽

Yuan Huang ◽

Yuchao Zhang ◽

Xiangtai Zeng ◽

Mei Yan ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Cell Apoptosis ◽

Downstream Target ◽

Normal Tissues ◽

Physiological Processes ◽

Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

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si-SNHG5-FOXF2 inhibits TGF-β1-induced fibrosis in human primary endometrial stromal cells by the Wnt/β-catenin signalling pathway

Stem Cell Research & Therapy ◽

10.1186/s13287-020-01990-3 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Limin Liu ◽

Guobin Chen ◽

Taoliang Chen ◽

Wenjuan Shi ◽

Haiyan Hu ◽

...

Keyword(s):

Cell Proliferation ◽

Stromal Cells ◽

Target Genes ◽

Cell Model ◽

Ex Vivo ◽

Signalling Pathway ◽

Endometrial Stromal Cells ◽

Downstream Target ◽

Related Proteins ◽

Tgf Β1

Abstract Background Intrauterine adhesions (IUAs) are manifestations of endometrial fibrosis characterized by inflammation and fibrinogen aggregation in the extracellular matrix (ECM). The available therapeutic interventions for IUA are insufficiently effective in the clinical setting for postoperative adhesion recurrence and infertility problems. In this study, we investigated whether si-SNHG5-FOXF2 can serve as a molecular mechanism for the inhibition of IUA fibrosis ex vivo. Methods FOXF2, TGF-β1 and collagen expression levels were measured by microarray sequencing analysis in three normal endometrium groups and six IUA patients. We induced primary human endometrial stromal cells (HESCs) into myofibroblasts (MFs) to develop an IUA cell model with various concentrations of TGF-β1 at various times. Downstream target genes of FOXF2 were screened by chromatin immunoprecipitation combined with whole-genome high-throughput sequencing (ChIP-seq). We investigated ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related proteins in primary HESCs with FOXF2 downregulation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting (WB), immunohistochemistry (IHC), flow cytometry, ethylenediurea (EdU) and CCK8 assays. We identified long noncoding RNAs (lncRNA) SNHG5 as the upstream regulatory gene of FOXF2 through RNA immunoprecipitation (RIP), RNA pulldown and fluorescence in situ hybridization (FISH). Finally, we examined FOXF2 expression, ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related proteins in primary HESCs upon FOXF2 downregulation. Results FOXF2 was highly expressed in the endometrium of patients with IUA. Treatment of primary HESCs with 10 ng/ml TGF-β1 for 72 h was found to be most effective for developing an IUA cell model. FOXF2 regulated multiple downstream target genes, including collagen, vimentin (VIM) and cyclin D2/DK4, by ChIP-seq and ChIP-PCR. FOXF2 downregulation inhibited TGF-β1-mediated primary HESC fibrosis, including ECM formation, cell proliferation and Wnt/β-catenin signalling pathway-related protein expression. We identified lncRNA SNHG5 as an upstream gene that directly regulates FOXF2 by RIP-seq, qRT-PCR, WB and FISH. SNHG5 downregulation suppressed FOXF2 expression in the IUA cell model, resulting in synergistic repression of the Wnt/β-catenin pathway, thereby altering TGF-β1-mediated ECM aggregation in endometrial stromal cells ex vivo. Conclusions Regulation of the Wnt/β-catenin signalling pathway and ECM formation by si-SNHG5-FOXF2 effectively inhibited the profibrotic effect of TGF-β1 on primary HESCs. This finding can provide a molecular basis for antagonizing TGF-β1-mediated fibrosis in primary HESCs.

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CDK Inhibitor p18INK4c Is a Downstream Target of GATA3 and Restrains Mammary Luminal Progenitor Cell Proliferation and Tumorigenesis

Cancer Cell ◽

10.1016/j.ccr.2009.03.004 ◽

2009 ◽

Vol 15 (5) ◽

pp. 389-401 ◽

Cited By ~ 49

Author(s):

Xin-Hai Pei ◽

Feng Bai ◽

Matthew D. Smith ◽

Jerry Usary ◽

Cheng Fan ◽

...

Keyword(s):

Cell Proliferation ◽

Progenitor Cell ◽

Cdk Inhibitor ◽

Luminal Progenitor ◽

Downstream Target ◽

Luminal Progenitor Cell ◽

Progenitor Cell Proliferation

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oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27kip1 signaling: opposite effects of oxLDL and cholesterol loading

AJP Cell Physiology ◽

10.1152/ajpcell.00249.2016 ◽

2017 ◽

Vol 313 (3) ◽

pp. C340-C351 ◽

Cited By ~ 11

Author(s):

Chongxu Zhang ◽

Crystal Adamos ◽

Myung-Jin Oh ◽

Jugajyoti Baruah ◽

Manuela A. A. Ayee ◽

...

Keyword(s):

Cell Proliferation ◽

Kinase Inhibitor ◽

Oxidized Ldl ◽

Endothelial Cell Proliferation ◽

Dependent Manner ◽

Akt Inhibitor ◽

Aortic Endothelial Cells ◽

Akt Phosphorylation ◽

Downstream Target ◽

Underlying Mechanisms

Oxidized modifications of LDL (oxLDL) play a key role in the development of endothelial dysfunction and atherosclerosis. However, the underlying mechanisms of oxLDL-mediated cellular behavior are not completely understood. Here, we compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu2+-oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human aortic endothelial cells (HAECs). Cu2+-oxLDL enhanced HAECs’ proliferation in a dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also enhanced HAEC proliferation. Mechanistically, both Cu2+-oxLDL and LPO-oxLDL enhance HAEC proliferation via activation of Rho, Akt phosphorylation, and a decrease in the expression of cyclin-dependent kinase inhibitor 1B (p27kip1). Both Cu2+-oxLDL or LPO-oxLDL significantly increased Akt phosphorylation, whereas an Akt inhibitor, MK2206, blocked oxLDL-induced increase in HAEC proliferation. Blocking Rho with C3 or its downstream target ROCK with Y27632 significantly inhibited oxLDL-induced Akt phosphorylation and proliferation mediated by both Cu2+- and LPO-oxLDL. Activation of RhoA was blocked by Rho-GDI-1, which also abrogated oxLDL-induced Akt phosphorylation and HAEC proliferation. In contrast, blocking Rac1 in these cells had no effect on oxLDL-induced Akt phosphorylation or cell proliferation. Moreover, oxLDL-induced Rho/Akt signaling downregulated cell cycle inhibitor p27kip1. Preloading these cells with cholesterol, however, prevented oxLDL-induced Akt phosphorylation and HAEC proliferation. These findings provide a new understanding of the effects of oxLDL on endothelial proliferation, which is essential for developing new treatments against neovascularization and progression of atherosclerosis.

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Angiogenin-Stimulated rRNA Transcription Is Essential for Initiation and Survival of AKT-Induced Prostate Intraepithelial Neoplasia

Molecular Cancer Research ◽

10.1158/1541-7786.mcr-08-0137 ◽

2009 ◽

Vol 7 (3) ◽

pp. 415-424 ◽

Cited By ~ 28

Author(s):

Soichiro Ibaragi ◽

Norie Yoshioka ◽

Hiroko Kishikawa ◽

Jamie K. Hu ◽

Peter M. Sadow ◽

...

Keyword(s):

Intraepithelial Neoplasia ◽

Prostate Intraepithelial Neoplasia ◽

Rrna Transcription

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LncRNA ADAMTS9-AS2 in osteosarcoma inhibits cell proliferation and enhances paclitaxel sensitivity by suppressing microRNA-130a-5p

European Journal of Inflammation ◽

10.1177/2058739220934560 ◽

2020 ◽

Vol 18 ◽

pp. 205873922093456 ◽

Cited By ~ 1

Author(s):

Xiaoqiang Ren ◽

Jingwei Cai ◽

Yongheng Wang ◽

Xingren Zhu ◽

Jun Qian ◽

...

Keyword(s):

Cell Proliferation ◽

Noncoding Rna ◽

Target Gene ◽

Luciferase Reporter ◽

Critical Function ◽

Downstream Target ◽

Downstream Target Gene ◽

Proliferation Ability ◽

Polymerase Chain ◽

Qpcr Experiment

Introduction: Long noncoding RNA ADAMTS9-AS2 (lncRNA ADAMTS9-AS2) has critical function in tumor growth and drug resistance of various cancers. However, the role and mechanism of lncRNA ADAMTS9-AS2 in osteosarcoma (OS) is still unclear. Methods: The expression of lncRNA ADAMTS9-AS2 and MicroRNAs-130a-5p (miR-130a-5p) was detected by real-time polymerase chain reaction (RT-qPCR) experiment. In addition, we used the plasmids transfection to construct the lncRNA ADAMTS9-AS2 overexpressed OS cell lines. Subsequently, the cell proliferation ability and the sensitivity to paclitaxel (PTX) in OS cells upon up-regulating lncRNA ADAMTS9-AS2 expression were analyzed via CCK-8 assay, while Western blotting experiment was performed to detect the regulatory mechanism. Results: We found that lncRNA ADAMTS9-AS2 was down-regulated in OS tissues, and the OS patients with lncRNA ADAMTS9-AS2 downexprssion were usually accompanied with a poor prognosis. Subsequently, we discovered that up-regulation of lncRNA ADAMTS9-AS2 inhibited cell proliferation and increased the sensitivity to PTX in OS cells. Interestingly, the Western blot results showed that overexpression of lncRNA ADAMTS9-AS2 could lead to PTEN expression increased, with PI3K and p-AKT expression decreased, indicating that lncRNA ADAMTS9-AS2 could increase the OS cell sensitivity to PTX via regulating PTEN-PI3K/AKT pathway. Furthermore, we identified MicroRNAs-130a-5p (miR-130a-5p) as the downstream target gene of lncRNA ADAMTS9-AS2, which was further confirmed by the luciferase reporter assay. More importantly, our data revealed that miR-130a-5p mimics could partly reverse the influence on cell proliferation and drug sensitivity induced by lncRNA ADAMTS9-AS2 overexpression. Conclusion: LncRNA ADAMTS9-AS2 exerts its anti-carcinogenesis function by sponging miR-130a-5p, which might be a new therapeutic target for OS treatment.

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