miR-938 Promotes the Proliferation and Invasion of Prostate Cancer Through Targeting Pleckstrin Homology (PH) Domain Leucine-Rich-Repeats Protein Phosphatase 2 and Forkhead Box O3

2019 ◽  
Vol 9 (5) ◽  
pp. 583-591
Author(s):  
Xin Deng ◽  
Fengye Wang ◽  
Qianjin Zhang ◽  
Xuejian Yang ◽  
Hao Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Phosphatase ◽  
Mrna Level ◽  
Signal Pathway ◽  
Migration And Invasion ◽  
Ph Domain ◽  
Pleckstrin Homology ◽  
Forkhead Box ◽  
Protein Phosphatase 2 ◽  
Leucine Rich Repeats

miR-938 is generally reported to be up-regulated in various cancers, which affect the tumor progression. In the present study, we investigated the biological role and underlying mechanisms of miR-938 in prostate cancer (PCa). PCa is the most common malignant tumor in males with markedly increasing incidence in recent years. Up-regulation of miR-938 occurred in PCa tissues and cell lines at mRNA level. Functional assays were established to demonstrate that miR-938 mimics significantly promoted the proliferation, migration and invasion of PCa cells, while knockdown of miR-938 led to the inhibition. Luciferase activity assay suggested miR-938 directly bound to the 3 UTR of PHLPP2 (Pleckstrin Homology (PH) domain Leucine-rich-repeats Protein Phosphatase 2) and FOXO3 (Forkhead box O3). Our results also showed that the regulation activity of miR-938 on progression of PCa was partially through its negative regulation on PHLPP2 and FOXO3. Our results deciphered the mechanism through which miR-938 promoted the progression of PCa by activation of PI3K/AKT signal pathway. Together, inactivation of PI3K/AKT signal pathway through down-regulation of miR-938 could be an important mechanism in inhibiting PCa progression, thus shedding light on the development of novel anti-tumor therapies for treatment of PCa.

scholarly journals MicroRNA-527 Induces Proliferation and Cell Cycle in Esophageal Squamous Cell Carcinoma Cells by Repressing PH Domain Leucine-Rich-Repeats Protein Phosphatase 2

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582092868 ◽  
Author(s):  
Qingjie Xian ◽  
Ronglei Zhao ◽  
Juanjuan Fu
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Protein Phosphatase ◽  
Ph Domain ◽  
Gene Reporter Assay ◽  
Protein Phosphatase 2

Increasing evidence indicated that microRNAs served dominant roles in carcinogenesis and cancer progression by targeting potential downstream genes. In our study, we found that miR-527 was an upregulated expression in human esophageal squamous cell carcinoma (ESCC) cells and tissues. Furthermore, overexpression of miR-527 promoted cell proliferation and colony formation, enhanced anchorage-independent growth ability, and contributed to cell cycle. In addition, protein phosphatase 2 (PHLPP2) was identified as the direct downstream target gene of miR-527 and was confirmed by luciferase gene reporter assay. In summary, we concluded that miR-527 acted as an oncogenic microRNA in ESCC development by directly targeting PHLPP2 might be a novel therapeutic target for the treatment of ESCC.

scholarly journals Knockdown of Circular RNA hsa_circ_PVT1 Inhibited Laryngeal Cancer Progression via Preventing wnt4/β-Catenin Signaling Pathway Activation

2021 ◽  
Vol 9 ◽  
Author(s):  
Feng Yu ◽  
Ying Lin ◽  
Mao-Mao Ai ◽  
Guo-Jie Tan ◽  
Jia-Li Huang ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Laryngeal Cancer ◽  
Mrna Level ◽  
Circular Rna ◽  
Signal Pathway ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Pathway Activation ◽  
The Relationship ◽  
Apoptosis Level

AimTo explore the function and mechanism of circular has_circ_PVT1 on laryngeal cancer (LC).MethodsMicroarray chip was performed to screen the differential expression of circRNA. Western blot and qRT-PCR was employed to detect the protein and mRNA level. CCK-8, clone formation, cell cycle, wound healing, and Transwell assay were performed to detect the cell proliferation, migration, and invasion ability. Luciferase assay and Fish were used to confirm the relationship between circ_PVT1/CBX4 and miR-21-5p. Flow cytometry and TUNEL assay were carried out to assess the apoptosis level.ResultsThe upregulation of circ_PVT1 was found in LC tissues and cells. Silencing of circ_PVT1 inhibited LC progression via targeting miR-21-5p and indirectly controlling CBX4. Wnt4/β-catenin signal pathway was inactivated by inhibiting the expression of circ_PVT1.ConclusionKnockdown of circ_PVT1 prevented LC progression via targeting miR-21-5p/CBX4 by inhibiting wnt4/β-catenin signal pathway, which could provide a novel therapeutic target for LC.

scholarly journals Osteoblast-Induced Prostate Cancer Cell Migration and Invasion Is Mediated Through TGF-β1/SMAD2 Signal Pathway and Blocked by 17α-Estradiol

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1029-A1029
Author(s):  
Jian Shi ◽  
Lian Zhao ◽  
Brittany Duncan ◽  
Jie Su ◽  
Jale Manzo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Signal Pathway ◽  
Migration And Invasion ◽  
Osteoblast Cells ◽  
Cell Migration And Invasion ◽  
Tgf Β1 ◽  
Hfob Cell ◽  
Mcf 7 ◽  
Stimulation Of

Abstract Prostate cancer (PCa) is curable if it is diagnosed and treated in localized and regional stage. However, PCa outcome is poor once it has distant metastasis. Approximately 70% to 100% of PCa deaths have bone metastasis, which may be associated with a specific bone microenvironment. In this study, we investigated the effect and molecular mechanism of osteoblast cells on stimulation of PCa cell migration and invasion and examined the effectiveness of 17α-estradiol on blocking osteoblast-induced PCa cell migration and invasion using in vitro cell analysis. PCa cells (PC3, LNCaP and DU145), osteoblast hFOB, kidney CV-1, breast tumor MCF-7 and liver cancer Huh-7 cells (ATCC) were cultured in RMPI-1640 or DMEM media supplemented with or without fetal bovine serum (FBS) at 37 oC in a 5% CO2-humidified incubator. hFOB condition media (HCM) without FBS were collected at different times of hFOB cell culture. Transwell and wound-healing experiments were used to determine PCa cell migration and invasion. Cell migration and invasion in PC3, DU-145 and LNCaP PCa cells were markedly promoted by co-culturing hFOB osteoblast cells or HCM, but not by cells or condition media originated from kidney (CV-1), liver (Huh-7) and breast (MCF-7). Compared to other non-osteoblast cell conditioned media, HCM had much higher levels of several cytokines and chemokines including tumor growth factor (TGF) β1. Both HCM and TGF-β1 produced a dose- and time-dependent induction of PCa cell migration and invasion as well as SMAD2 phosphorylation without altering cell proliferation. These HCM and TGF-β1 effects were inhibited by a specific TGFβ receptor inhibitor, LY2157299, as well as by 17α-estradiol in a dose-dependent manner. Most intriguing, 17α-estradiol significantly inhibited the HCM and TGF-β1-induced PCa cell migration and invasion at very low nanomolar concentrations, presumably mediated through estrogen receptor β. These findings suggest that TGF-β1 is a major factor in mediating hFOB cell stimulation of PCa cell migration and invasion, and 17α-estradiol is a potential agent to block PCa cell bone metastasis, probably through inhibition of TGF-β1/SMAD2 signal pathway.

scholarly journals VEGF Induce Vasculogenic Mimicry of Choroidal Melanoma through the PI3k Signal Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Xiaoyan Xu ◽  
Yao Zong ◽  
Yunxia Gao ◽  
Xiangrong Sun ◽  
Han Zhao ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Gene Deletion ◽  
Mrna Level ◽  
Vasculogenic Mimicry ◽  
Choroidal Melanoma ◽  
Signal Transduction Pathway ◽  
Signal Pathway ◽  
Migration And Invasion ◽  
Vegf Gene ◽  
Endothelial Growth Factor

Purpose. To explore the effect of VEGF (vascular endothelial growth factor) on the vasculogenic mimicry (VM) formation of Choroidal Melanoma (CM) through PI3k signal pathway, to find novel targets for CM therapy. Methods. This research investigated the molecular mechanism of VEGF promoting VM formation of CM. First, we evaluated the expressions of VEGF in 20 CM specimens by immunohistochemical determination. Then we detected expressions of VEGF, AKT, MT1-MMP, MMP2, and MMP9 of OCM-1 in hypoxia. siRNA was used to inhibit the expression of VEGF, to realize the control of the VM formation. The VM formation was evaluated through wound healing assay, transwell assay, and apoptosis. And then we testify the correlation of the VM and the factors in protein and mRNA level preliminarily. Results. VEGF protein was expressed in CM in all 20 cases of CM, especially along the VM. In hypoxia, the expression of VEGF in OCM-1 increased significantly. VEGF gene deletion reduced the proliferation, migration, and invasion of OCM-1. VEGF gene deletion impaired the expression of invasive associated genes like VEGF, p-AKT, AKT, MT1-MMP, MMP2, and MMP9. These results indicate that VEGF induce VM formation in CM by activating PI3K/AKT signaling pathway. Conclusions. VEGF promoted VM formation by the PI3K signal transduction pathway, indicating a molecular mechanism which may be used to develop new therapeutic targets for the clinical treatment of CM.

scholarly journals MicroRNA-149 Increases the Sensitivity of Colorectal Cancer Cells to 5-Fluorouracil by Targeting Forkhead Box Transcription Factor FOXM1

2016 ◽  
Vol 39 (2) ◽  
pp. 617-629 ◽  
Author(s):  
Xiaobei Liu ◽  
Tao Xie ◽  
Xiaobei Mao ◽  
Lijun Xue ◽  
Xiaoyuan Chu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcription Factor ◽  
Mrna Level ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Forkhead Box ◽  
Forkhead Box M1 ◽  
Colorectal Cancer Cells ◽  
Potential Strategy

Background/Aims: Previously, we have shown that microRNA (miR)-149 suppresses the migration and invasion of colorectal cancer (CRC) cells by targeting forkhead box transcription factor (FOXM1). However, the roles of miR-149 in the chemoresistance of CRC cells to 5-Fluorouracil (5-FU) is unclear. The aim of this study is to investigate whether miR-149 targets FOXM1 to regulate the 5-FU resistance of CRC. Methods: The qRT-PCR assay was performed to detect the expression of miR-149 in 5-FU-resistant CRC cells (HCT-8/5-FU and LoVo/5-FU) and their parental CRC cells (HCT-8 and LoVo). Also, the effects of miR-149 expression on the sensitivity of CRC cells to 5-FU were determined by gain- and loss-of-function assays. Finally, whether miR-149 regulates the 5-FU resistance of CRC cells by targeting the mammalian Forkhead Box M1 (FOXM1) was investigated. Results: The expression of miR-149 was significantly downregulated in 5-FU-resistant CRC cells in comparison with their parental CRC cells. Re-expression of miR-149 could enhance the 5-FU sensitivity of 5-FU-resistant CRC cells by increasing 5-FU-inducing apoptosis, while downregulation of miR-149 could decrease the 5-FU sensitivity of parental CRC cells by decreasing 5-FU-inducing apoptosis. In addition, the luciferase assay indicated that miR-149 could bind to the 3'-UTR sequence of FOXM1 mRNA. The silencing of FOXM1 could mimic the effect of miR-149 upregulation on the 5-FU resistance of 5-FU-resistant CRC cells. Furthermore, the expression of miR-149 in the 5-FU-responding CRC tissues was significantly higher than that in the non-responding tissues and inversely correlated with FOXM1 mRNA level. Conclusions: MiR-149 reverses the resistance of CRC cells to 5-FU by directly targeting FOXM1. Thus, targeting miR-149/FOXM1 signaling will be a potential strategy in the treatment of 5-FU-chemoresistant CRC.

Sign in / Sign up

Export Citation Format

Share Document