scholarly journals microRNA-613 exerts anti-angiogenic effect on nasopharyngeal carcinoma cells through inactivating the AKT signaling pathway by down-regulating FN1

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Ru Gao ◽  
Qiaolei Feng ◽  
Guolin Tan
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Nude Mice ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Angiogenic Effect ◽  
Regulatory Effects ◽  
Unclear Etiology

Abstract Background: Nasopharyngeal carcinoma (NPC) is a disease highly sensitive to radiotherapy with the unclear etiology. However, the specific effects of microRNA-613 (miR-613) on NPC still remain elusive. Therefore, the present study probes into the underlying mechanism of miR-613 in NPC via AKT signaling pathway by regulating Fibronectin 1 (FN1). Methods: First, microarray analysis was used to screen differentially expressed genes (DEGs) and regulatory miRs associated with NPC. Next, miR-613 and FN1 expression in NPC cells was determined, followed by verification of target relationship between miR-613 and FN1. With NPC cells exposed to miR-613 mimic, si-FN1 and LY294002 (inhibitor of AKT signaling pathway), the regulatory effects of miR-613 on proliferation, apoptosis, invasion, migration and angiogenesis of NPC cells were detected with ratio of B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax), Cleaved-caspase3, matrix metallopeptidase 2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), and cell adhesion molecule-1 (CD31) expression measured. Then, tumorigenesis and MVD were determined after Xenograft in nude mice. Results: FN1 modulated by miR-613 was critical for NPC via the AKT signaling pathway. NPC cells exhibited down-regulated miR-613 and up-regulated FN1. Besides, miR-613 was verified to target FN1. Moreover, overexpressed miR-613, silenced FN1 or LY294002 treatment suppressed proliferation, invasion, migration, and angiogenesis in NPC cells, which was indicated by reduced expression of AKT, mTOR, MMP-2, MMP-9, VEGF, and CD31 as well as decreased ratio of Bcl-2/Bax and increased expression of Cleaved-caspase3. Furthermore, cell apoptosis was promoted and tumorigenesis and MVD in nude mice were inhibited with overexpression of miR-613, silenced FN1 or LY294002 treatment. Conclusion: Taken together, miR-613 inhibits angiogenesis in NPC cells through inactivating FN1-dependent AKT signaling pathway.

scholarly journals Sulforaphane Attenuates Endometriosis in Rat Models Through Inhibiting PI3K/Akt Signaling Pathway

Dose-Response ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 155932581985553 ◽  
Author(s):  
Aixiu Zhou ◽  
Yiting Hong ◽  
Yuchun Lv
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Akt Signaling Pathway ◽  
Tnf Α ◽  
Ifn Γ

Sulforaphane exerts anti-inflammatory activity in inflammatory diseases. The endometriosis (EM) is accompanied by chronic inflammation. The present study aims to explore the therapeutic effects of sulforaphane on EM and its underlying mechanism. An EM rat model was established by transplantation of autologous fragments. The rats were intragastrically administered sulforaphane (5 mg/kg, 15 mg/kg, and 30 mg/kg) for 3 weeks. The volumes of endometriotic foci and adhesion score were calculated at the end of the experiment. Levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA). Expressions of VEGF, B-cell lymphoma/leukemia 2 (Bcl-2), Bax, cleaved caspase-3, PI3K, and Akt in endometrial tissue were determined by Western blotting. Relative expressions of PI3K and Akt were determined by quantitative polymerase chain reaction. Posttreatment of sulforaphane dose-dependently decreased the volumes of endometriotic foci and adhesion score in EM model. Additionally, posttreatment of sulforaphane inhibited levels of IL-6, IL-10, TNF-α, IFN-γ, and VEGF in peritoneal fluid and plasma. Posttreatment of sulforaphane regulated the expressions of VEGF, bcl-2, Bax, and cleaved Caspase-3 in EM model. The underlying mechanism revealed that sulforaphane attenuated EM in the rat model by inhibition of PI3K/Akt signaling pathway.

scholarly journals Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao-jun Gou ◽  
Huan-huan Bai ◽  
Li-wei Liu ◽  
Hong-yu Chen ◽  
Qi Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Nude Mice ◽  
Breast Cancer Cells ◽  
Akt Signaling ◽  
Asiatic Acid ◽  
Akt Signaling Pathway ◽  
Xenografted Tumor

Objective. To explore the ability of asiatic acid to interfere with the invasion and proliferation of breast cancer cells by inhibiting WAVE3 expression and activation through the PI3K/AKT signaling pathway. Methods. The MDA-MB-231 cells with strong invasiveness were screened by transwell assay, and plasmids with high expression of WAVE3 were constructed for transfection. The transfection effect and protein expression level of plasmids were verified by PCR and WB. The effects of asiatic acid on cell proliferation and invasion were investigated by flow cytometry. The xenografted tumor models in nude mice were established to study the antitumor activity of asiatic acid. Results. Asiatic acid significantly inhibited the activity of MDA-MB-231 cells, and the expression level of WAVE3 increased significantly in the tissue of ductal carcinoma in situ and was lower than that in the metastasis group. After plasmid transfection, the mRNA and protein expression of WAVE3 increased significantly in the cells. Asiatic acid at different concentrations had an impact on cell apoptosis and invasion and could significantly inhibit the expression of WAVE3, P53, p-PI3K, p-AKT, and other proteins. The T/C(%) of asiatic acid (50 mg/kg) for MDA-MB-231(F10) xenografted tumor in nude mice was 46.33%, with a tumor inhibition rate of 59.55%. Asiatic acid could significantly inhibit the growth of MDA-MB-231 (F10) xenografted tumors in nude mice (p<0.05). Conclusions. Asiatic acid interferes with the ability of breast cancer cells to invade and proliferate by inhibiting WAVE3 expression and activation and the mechanism of action may be related to the PI3K/AKT signaling pathway.

MicroRNA-134 inhibits tumor stem cell migration and invasion in oral squamous cell carcinomas via downregulation of PI3K-Akt signaling pathway by inhibiting LAMC2 expression

2020 ◽  
Vol 29 (1) ◽  
pp. 51-67 ◽  
Author(s):  
Yong-Mei Zhou ◽  
Yi-Lin Yao ◽  
Wei Liu ◽  
Xue-Min Shen ◽  
Lin-Jun Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Nude Mice ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Tumor Stem Cells ◽  
Akt Signaling Pathway

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the mouth. Some studies have found that multiple microRNAs (miRs) participate in OSCC physiological and pathological processes. METHODS: We explored the mechanism of action of miR-134 in OSCC involving the PI3K-Akt signaling pathway. Different bioinformatics methods were used to analyze the potential genes and their related miRs in OSCC. Tumor stem cells were separated from OSCCs through magnetic cell sorting. Regulatory pattern between miR-134 and LAMC2 in OSCC was evaluated by ectopic expression, knockdown and reporter assay experiments. The expression of miR-134, LAMC2, genes in PI3K-Akt signaling pathway, and apoptosis-related genes was detected. Cell proliferation was assessed by MTT assay, cell invasion by scratch test, cell migration by Transwell assay, cell cycle and apoptosis by flow cytometry, and cell growth and migration by xenograft tumor in nude mice. LAMC2 was predicted as the crucial factor related to OSCC using different chip data, and miR-134 was predicted to specifically bind LAMC2 in all five databases. RESULTS: Overexpressed miR-134 or silenced LAMC2 was observed to inhibit cell proliferation, migration, invasion of OSCC cells, growth of subcutaneous xenograft in nude mice, as well as promote OSCC cell apoptosis. LAMC2, a target gene of miR-134, decreased following miR-134 promotion, while the PI3K-Akt signaling pathway was inactivated following LAMC2 knockdown. Furthermore, we also observed that the effect of overexpressed miR-134 was enhanced when LAMC2 was knocked down. CONCLUSIONS: Taken together, these findings suggest that miR-134-mediated direct downregulation of LAMC2 inhibits migration and invasion of tumor stem cells in OSCC by suppressing the PI3K-Akt signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document