scholarly journals Midkine promotes glioblastoma progression via PI3K-Akt signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Beiquan Hu ◽  
Chao Qin ◽  
Li Li ◽  
Lei Wei ◽  
Xianlun Mo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Lines ◽  
Regulatory Network ◽  
Poor Prognosis ◽  
Transcriptional Regulatory Network ◽  
Akt Signaling ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Aberrant Expression

Abstract Background Our previous bioinformatics-based study found that midkine (MDK) was associated with poor prognosis of glioblastoma (GBM). However, the mechanism of MDK in GBM remains elusive. Methods A public GBM-related dataset and GBM tissues from our center were used validate the aberrant expression of MDK in GBM at the RNA and protein levels. The relationship between MDK expression and survival of GBM patients was also explored through survival analysis. Subsequently, we identified MDK-related GBM-specific genes using differential expression analysis. Functional enrichment analyses were performed to reveal their potential biological functions. CCK-8, 5-ethynyl-2′-deoxyuridine, and Matrigel-transwell assays were performed in GBM cell lines in which MDK was knocked out or overexpressed in order assess the effects of MDK on proliferation, migration, and invasion of GBM cells. Western blotting was performed to detect candidate proteins. Results Our study showed MDK is a promising diagnostic and prognostic biomarker for GBM because it is highly expressed in the disease and it is associated with poor prognosis. MDK is involved in various cancer-related pathways, such as PI3K-Akt signaling, the cell cycle, and VEGF signaling. A comprehensive transcriptional regulatory network was constructed to show the potential pathways through which MDK may be involved in GBM. In vitro, Overexpression of MDK augmented proliferation, migration, and invasion of GBM cell lines, whereas suppression of MDK led to the opposite effects. Furthermore, our study confirmed that MDK promotes the progression of GBM by activating the PI3K-Akt signaling pathway. Conclusions Our present study proposes that MDK promotes GBM by activating the PI3K-Akt signaling pathway, and it describes a potential regulatory network involved.

scholarly journals CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tao Jiang ◽  
Hongyu Wang ◽  
Lianyu Liu ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
In Situ Hybridization ◽  
Signaling Pathway ◽  
Clinical Significance ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Aberrant Expression

Abstract Background Accumulating studies have revealed that aberrant expression of circular RNAs (circRNAs) is widely involved in the tumorigenesis and progression of malignant cancers, including colorectal cancer (CRC). Nevertheless, the clinical significance, levels, features, biological function, and molecular mechanisms of novel circRNAs in CRC remain largely unexplored. Methods CRC-related circRNAs were identified through bioinformatics analysis and verified in clinical specimens by qRT–PCR and in situ hybridization (ISH). Then, in vitro and in vivo experiments were performed to determine the clinical significance of, functional roles of, and clinical characteristics associated with circIL4R in CRC specimens and cells. Mechanistically, RNA pull-down, fluorescence in situ hybridization (FISH), luciferase reporter, and ubiquitination assays were performed to confirm the underlying mechanism of circIL4R. Results CircIL4R was upregulated in CRC cell lines and in sera and tissues from CRC patients and was positively correlated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that circIL4R promotes CRC cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. Mechanistically, circIL4R was regulated by TFAP2C and competitively interacted with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway and consequently facilitate CRC progression. Conclusions Our findings demonstrate that upregulation of circIL4R plays an oncogenic role in CRC progression and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment.

scholarly journals TMEM60 Promotes the Proliferation and Migration and Inhibits the Apoptosis of Glioma through Modulating AKT Signaling

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Jingwen Wu ◽  
Xinghua Tang ◽  
Xuejuan Yu ◽  
Xiaoli Zhang ◽  
Wenjun Yang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Western Blotting ◽  
Cell Apoptosis ◽  
Glioma Cell ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Glioma Cell Lines

Glioma is a highly fatal malignancy with aggressive proliferation, migration, and invasion metastasis due to aberrant genetic regulation. This work aimed to determine the function of transmembrane protein 60 (TMEM60) during glioma development. The level of TMEM60 in glioma tissues and normal tissues and its correlation with glioma prognosis were checked in The Cancer Genome Atlas (TCGA) database. The levels of TMEM60 in glioma cell lines and normal astrocytes were determined by quantitative real-time PCR and western blotting assay. TMEM60 knockdown and overexpression were conducted, followed by detection of cell viability, migration, invasion, and apoptosis. CCK-8 and colony formation assay were adopted to detect cell viability proliferation. Transwell assay was performed to measure cell migration and invasion. Cell apoptosis was evaluated by flow cytometry. The alternation of key proteins in the PI3K/Akt signaling pathway was measured by western blotting. TMEM60 expression was significantly higher in glioma tissues than that in the healthy control and was correlated with poor overall survival of patients. The protein and mRNA levels of TMEM60 were both elevated in glioma cell lines in comparison with the normal cell lines. Elevated level of TMEM60 led to enhanced proliferation, migration, and invasion and suppressed cell apoptosis. TMEM60 promoted the activation of PI3K/Akt signaling. Our data suggested that TMEM60 plays an oncogenic role in glioma progression via activating the PI3K/Akt signaling pathway.

scholarly journals Silence of long non-coding RNA KCNQ1OT1 inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells through PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Hongliang Mei ◽  
Zhiguo Yu ◽  
Guanqi Zhang ◽  
Zhiyuan Huang ◽  
Hanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Negative Impact ◽  
Akt Signaling ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Potential Biomarker

Abstract Background: KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) has been reported to be associated with hepatocellular carcinoma (HCC), which is considered as one of the most common cancers worldwide. However, the mechanism of action of KCNQ1OT1 in human HCC has not been fully explained. In this study, we aimed to explore the functional role and the potential mechanism of KCNQ1OT1 in human HCC.Methods: First, we analyzed the expression levels of KCNQ1OT1 in HCC tissues in starBase database and detected the expression of KCNQ1OT1 in HCC cell lines by quantitative real-time polymerase chain reaction assays. Next, we analyzed the role of KCNQ1OT1 in migration, invasion and proliferation of HCC by scratch wound healing, transwell and cell counting kit-8 assays. Finally, we analyzed the potential interrelationship between KCNQ1OT1 and PI3K/AKT signaling pathway through western blot assays.Results: Based on bioinformatics analyses, we found that KCNQ1OT1 was highly expressed in HCC tissues and its high expression was associated with a poor prognosis in HCC patients. We also confirmed an abnormal increase in the expression of KCNQ1OT1 in HCC cell lines. KCNQ1OT1 knockdown was found to have a negative impact on proliferation, migration and invasion of HCC cells. In addition, interference with the expression of KCNQ1OT1 reduced the phosphorylation level of AKT and the protein level of PI3K, indicating the association of KCNQ1OT1 with the PI3K/AKT signaling pathway.Conclusions: Collectively, this study confirmed the important role of KCNQ1OT1 in promoting HCC growth and revealed the inhibitory effect of KCNQ1OT1 on the PI3K/AKT signaling pathway. This work may contribute to a better understanding of HCC progression and provide a potential biomarker for HCC.

scholarly journals FERMT1 knockdown inhibits oral squamous cell carcinoma cell epithelial-mesenchymal transition by inactivating the PI3K/AKT signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiao Wang ◽  
Qianqian Chen
Keyword(s):  
Oral Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Western Blotting ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background The metastasis of oral cancer is one of the main causes of death. However, the mechanisms underlying oral cancer metastasis have not been completely elucidated. Fermitin family member 1 (FERMT1) plays an -oncogene role in many cancers; however, the role of FERMT1 in oral squamous cell cancer (OSCC) remains unclear. Methods In this study, OSCC cells were treated with 5 ng/ml recombinant human Transforming growth factor-β1 (TGF-β1) protein. FERMT1 expression was measured in OSCC cell lines by RT-qPCR and western blotting. The effect of FERMT1 knockdown on the migration and invasion of OSCC cells was evaluated by Transwell assay. The epithelial-mesenchymal transition (EMT) and PI3K/AKT signaling pathway-related mRNA expression and protein levels were assessed by RT-qPCR and western blotting. Results We found that FERMT1 expression was elevated in TGF-β1-induced OSCC cell lines, and knockdown of FERMT1 inhibited the migration and invasion in TGF-β1-induced OSCC cells. FERMT1 silencing inhibited vimentin, N-cadherin, matrix metalloproteinase 9 (MMP-9) expression and promoted E-cadherin expression, suggesting that FERMT1 silencing inhibited EMT in TGF-β1-induced OSCC cells. Furthermore, FERMT1 silencing inactivated the PI3K/AKT signaling pathway in TGF-β1-induced OSCC cells. Activation of the PI3K/AKT signaling pathway reversed the effect of FERMT1 silencing on OSCC cell migration, invasion, and EMT. Conclusions FERMT1 silencing inhibits the migration, invasion, and EMT of OSCC cells via inactivation of the PI3K/AKT signaling pathway, suggesting that FERMT1 is a novel and potential therapeutic target for anti-metastatic strategies for OSCC.

scholarly journals CORO1C is Associated With Poor Prognosis and Promotes Metastasis Through PI3K/AKT Pathway in Colorectal Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Zongxia Wang ◽  
Lizhou Jia ◽  
Yushu sun ◽  
Chunli Li ◽  
Lingli Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Akt Signaling ◽  
Actin Binding ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Related Proteins

Trophoblast cell surface protein 2 (Trop2) is one of the cancer-related proteins that plays a vital role in biological aggressiveness and poor prognosis of colorectal cancer (CRC). The study of the Trop2 related network is helpful for us to understand the mechanism of tumorigenesis. However, the effects of the related proteins interacting with Trop2 in CRC remain unclear. Here, we found that coronin-like actin-binding protein 1C (CORO1C) could interact with Trop2 and the expression of CORO1C in CRC tissues was higher than that in paracarcinoma tissues. The expression of CORO1C was associated with histological type, lymph node metastasis, distant metastasis, AJCC stage, venous invasion, and perineural invasion. The correlation between CORO1C expression and clinical characteristics was analyzed demonstrating that high CORO1C expression in CRC patients were associated with poor prognosis. Furthermore, CORO1C knockdown could decrease the cell proliferation, colony formation, migration and invasion in vitro and tumor growth in vivo. The underlying mechanisms were predicted by bioinformatics analysis and verified by Western blotting. We found that PI3K/AKT signaling pathway was significantly inhibited by CORO1C knockdown and the tuomr-promoting role of CORO1C was leastwise partly mediated by PI3K/AKT signaling pathway. Thus, CORO1C may be a valuable prognostic biomarker and drug target in CRC patients.

scholarly journals The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linwen Zhu ◽  
Zhe Li ◽  
Xiuchong Yu ◽  
Yao Ruan ◽  
Yijing Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Qrt Pcr

Abstract Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.

scholarly journals Girdin regulates the migration and invasion of glioma cells via the PI3K-Akt signaling pathway

2015 ◽  
Vol 12 (4) ◽  
pp. 5086-5092 ◽  
Author(s):  
WEIMIN NI ◽  
YAN FANG ◽  
LEI TONG ◽  
ZHAOXUE TONG ◽  
FUXIN YI ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Glioma Cells ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway

scholarly journals PI3K/AKT Signaling Pathway Mediates the Proliferation, Migration and Invasion of Papillary Craniopharyngioma Cells

2020 ◽  
Author(s):  
Lin Zhou ◽  
Cheng Xing Yang ◽  
Lin Chun Fang ◽  
You Yuan Bao ◽  
Zhi Gang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Specific Cell ◽  
Primary Cells ◽  
Akt Signaling Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Growth And Survival ◽  
Pi3k Signaling Pathway

Abstract Objective:Craniopharyngiomas are rare, histologically benign but clinically challenging neoplasms. Here, we aimed to interrogate the effect and significance of Phosphatidylinositol-3-kinase (PI3K) signaling pathway on papillary craniopharyngioma (PCP) cell growth and survival.Methods: We used Western blotting (WB) experiments to evaluate the expression of the PI3K/protein kinase B (AKT) in Craniopharyngiomas tissues, relative to health tissues. Primary tumor cells were obtained from fresh PCP samples by cell culture and then determined by cell morphology, immunofluorescence staining and expression of specific cell markers. In this study, PCP cell lines, isolated from fresh PCP samples, were treated with different concentrations of LY294002, a PI3K/AKT signaling inhibitor, to evaluate their proliferation, migration and invasion. We determined the cell proliferation using Cell Counting Kit-8 and colony formation. We then used flow cytometry to evaluate cell apoptosis and cell cycle. In addition, cell migration and invasion levels were determined by wound healing and Transwell assays, respectively.Results: Our data demonstrated that the expression of phosphorylated-PI3K/AKT was upregulated in human craniopharyngioma tissues compared to the normal control tissues. Immunofluorescence assays showed the presence of cytokeratin (pan CK) and vimentin protein (VIM) in the PCP primary cells. Furthermore, inhibition of PI3K/AKT signaling blocks the proliferation, migration and invasion of the PCP primary cells.Conclusions:Taken together, our data robustly demonstrates that the PI3K/AKT signaling pathway mediates the proliferation, migration and invasion of the PCP cells.

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