scholarly journals LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1313-1326 ◽  
Author(s):  
Yong  Chen ◽  
Wending Huang ◽  
Wei Sun ◽  
Biqiang Zheng ◽  
Chunmeng Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Cancer Metastasis ◽  
Soft Tissues ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Akt Signaling Pathway

Background/Aims: LncRNAs have been reported to be vital regulators of the progression of osteosarcoma, although the underlying mechanisms are not completely understood. Methods: The levels of MALAT1 and miR-129-5p expression were measured using qRT-PCR. Cell growth was determined using the CCK-8 and colony formation assays. Cell migration and invasion were detected using the wound healing and Transwell invasion assays, respectively. Tumor growth was determined with a xenograft model. Results: MALAT1 was significantly up-regulated in osteosarcoma tissues compared with adjacent non-tumor soft tissues. Overexpression of MALAT1 promoted osteosarcoma cell proliferation, migration, and invasion in vitro and enhanced tumor growth in a tumor xenograft mouse model. MALAT1 promoted osteosarcoma progression by modulating stem cell-like properties. Moreover, rescue experiment and luciferase reporter assay results indicated that MALAT1 modulates RET expression by sponging miR-129-5p in osteosarcomas. Furthermore, MALAT1 augmented the expression of downstream proteins of the RET-Akt pathway. MALAT1 was consistently significantly increased in osteosarcoma tissues and MALAT1 expression was positively correlated with tumor size and metastasis. High expression of MALAT1 was significantly associated with poor outcomes in patients with osteosarcomas. MALAT1 expression was positively related to RET and negatively related to miR-129-5p in osteosarcoma samples and xenograft tumors. MALAT1 functioned as an oncogenic lncRNA in osteosarcomas and was as an independent prognostic indicator. Conclusion: Our data revealed for the first time that MALAT1 increases stem cell-like properties by up-regulating RET via sponging miR-129-5p, and thus activates the PI3K-Akt signaling pathway and provides potential therapeutic targets for osteosarcoma treatment.

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 Knockdown of UBE2T Inhibits Osteosarcoma Cell Proliferation, Migration, and Invasion by Suppressing the PI3K/Akt Signaling Pathway

2016 ◽  
Vol 24 (5) ◽  
pp. 361-369 ◽  
Author(s):  
Yu Wang ◽  
Hui Leng ◽  
Hui Chen ◽  
Lei Wang ◽  
Nan Jiang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Akt Signaling Pathway ◽  
Inhibitory Effects ◽  
Study Results ◽  
Ubiquitin Conjugating Enzyme

Ubiquitin-conjugating enzyme E2T (UBE2T), a member of the E2 family, was found to be overexpressed in a great many cancers such as bladder cancer, lung cancer, and prostate cancer. However, there have been no reports on the role of UBE2T in osteosarcoma. In this study, we tried to make the effects of UBE2T on osteosarcoma clear. The study results showed that UBE2T was overexpressed in osteosarcoma tissues and cell lines. Moreover, UBE2T knockdown inhibited osteosarcoma cell proliferation, migration, and invasion. We also observed that UBE2T downregulation could suppress the activity of the PI3K/Akt signaling pathway. Therefore, we concluded that UBE2T exerted its inhibitory effects on osteosarcoma cells via suppressing the PI3K/Akt signaling pathway. These findings indicated that UBE2T may be a potential therapeutic target for osteosarcoma treatment.

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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