scholarly journals Downregulation of miR‑205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway

2017 ◽  
Author(s):  
Wei Chen ◽  
Kuan-Kei Kong ◽  
Xin-Ke Xu ◽  
Cheng Chen ◽  
Hui Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Mtor Signaling ◽  
Glioblastoma Cell ◽  
Mtor Signaling Pathway ◽  
Mesenchymal Transition

MiR-92a-3p promotes the malignant progression of hepatocellular carcinoma by mediating the PI3K/AKT/mTOR signaling pathway

2021 ◽  
Vol 27 ◽  
Author(s):  
Libing Wang ◽  
Mingxin Cui ◽  
Fengzhi Qu ◽  
Daming Cheng ◽  
Jingkun Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Mesenchymal Transition ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
Hcc Cells

Background: As one of the most common cancers in the world, hepatocellular carcinoma (HCC) usually has a poor prognosis. Many HCC patients are usually diagnosed at advanced stages. Therefore, new potential biomarkers for the diagnosis and prognosis of HCC are urgently needed. More and more studies have shown that miR-92a-3p can regulate the occurrence and development of a variety of cancers, but its clinical significance and molecular mechanism in HCC are still elusive. Here, we tried to clarify the regulatory mechanism of miR-92a-3p in HCC. Methods: In this study, we conducted qRT-PCR and revealed that miR-92a-3p was notably upregulated in HCC cells. MTT, flow cytometry, wound healing, Transwell invasion assays and western blot were conducted to uncover that overexpressed miR-92a-3p could boost the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells while inhibiting cell apoptosis. In addition, the proteins associated with PI3K/AKT/mTOR pathway were also detected by western blot. Results: It was suggested that miR-92a-3p could activate the PI3K/AKT/mTOR signaling pathway. Conclusion: These results suggest that miR-92a-3p plays a tumor-promoting role in HCC and may be a potential biomarker for the diagnosis and prognosis of HCC.

scholarly journals YTHDF1 promotes hepatocellular carcinoma progression via activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiangyuan Luo ◽  
Mengdie Cao ◽  
Fan Gao ◽  
Xingxing He
Keyword(s):  
Signaling Pathway ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Mtor Signaling ◽  
Gene Set Enrichment Analysis ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Promoting Effect ◽  
Mesenchymal Transition ◽  
Hcc Cells

Abstract Background N6-methyladenosine (m6A) modification, as the most abundant RNA modification, widely participates in the physiological process and is involved in multiple disease progression, especially cancer. YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) is a pivotal m6A “reader” protein, which has been reported in multiple cancers. However, the role and molecular mechanism of YTHDF1 in HCC are still not fully elucidated. Methods Based on various bioinformatics databases, q-RT PCR, western blot, and a tissue microarray containing 90 HCC samples, we examined the expression of YTHDF1 in HCC. Then, we applied the loss-of-function experiments to explore the role of YTHDF1 in HCC by in vitro and in vivo assays. Finally, we performed the gene set enrichment analysis (GSEA) to predict the potential signaling pathway of YTHDF1 involved in HCC and further verified this prediction. Results YTHDF1 was overexpressed in HCC and associated with HCC grade. Depletion of YTHDF1 markedly impaired the proliferation, migration, invasion, and cell cycle process of HCC cells. Mechanistically, YTHDF1 promoted the growth of HCC cells via activating the PI3K/AKT/mTOR signaling pathway. Moreover, we also demonstrated that the epithelial-mesenchymal transition (EMT) mediated the promoting effect of YTHDF1 on the migration and invasion of HCC cells. Conclusions YTHDF1 contributes to the progression of HCC by activating PI3K/AKT/mTOR signaling pathway and inducing EMT.

scholarly journals Cezanne enhances epithelial mesenchymal transition and prevents anthracycline-induced apoptosis via AKT/mTOR signaling in hepatocellular carcinoma

2021 ◽  
Author(s):  
Xiao-Ping Zhong ◽  
Jiahong Wang ◽  
Jie Mei ◽  
Lianghe Lu ◽  
Yihong Ling ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Mtor Inhibitor ◽  
Epithelial Mesenchymal Transition ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Mesenchymal Transition

Abstract Background Anthracycline resistance have hindered the efficacy of transcatheter arterial chemoembolization (TACE). Translational research is therefore in need to find potential combinations by studying the resistance mechanism of anthracycline. In our published work, we found Cezanne could predict the efficacy of adjuvant TACE (ad-TACE) and induce epithelium mesenchymal transition (EMT) in hepatocellular carcinoma (HCC). We hereby conduct a sequential investigation to reveal the role of Cezanne on EMT and its potential to retard resistance. Methods The response of Cezanne in patients treated with adjuvant TACE after hepatectomy was evaluated. Functional assays were used to examine the resistance function of Cezanne to anthracyclin. In-situ tumorigenesis models and intraperitoneal perfusion chemotherapy experiment were used for in vivo verification. Results High expression of Cezanne correlated to a better outcome. Multivariate analysis showed low expression of Cezanne and the application of postoperative ad-TACE therapy were independent prognostic risk factors. However, patient outcome was significantly shorter in high Cezanne group of ad-TACE patients. In vitro assays revealed that HCC functions were inhibited after overexpressing Cezanne (OE-Cezanne). After treated with epirubicin, however, OE-Cezanne cell lines did not respond to treatment. In vivo experiment was consistent with in vitro assays. Besides, high Cezanne transforms cell morphology and is correlated to the activation of EMT related genes. Gene set analysis showed that Cezanne can regulate PI3K/AKT/mTOR signaling pathway. Therefore, mTOR inhibitor Rapamycin can reverse the resisting effect of Cezanne on HCC cell lines. Conclusions Adjuvant anthracycline-based TACE treatment after curative surgery can reduce the recurrence rate in HCC patients. However, in patients with high Cezanne expression, the efficacy of TACE may be undermined by EMT inducement. We discovered Cezanne modulates EMT by activating the AKT/mTOR signaling pathway and provided evidence for the rationale of combining mTOR inhibitor with TACE to prevent recurrence in HCC patients.

scholarly journals Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 314
Author(s):  
Yu-Jen Wu ◽  
Wen-Chi Wei ◽  
Guo-Fong Dai ◽  
Jui-Hsin Su ◽  
Yu-Hwei Tseng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Signaling Pathway ◽  
Gelatin Zymography ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Mesenchymal Transition ◽  
Cell Metastasis ◽  
Study Results

Hepatocellular carcinoma (HCC) is the most common liver or hepatic cancer, accounting for 80% of all cases. The majority of this cancer mortality is due to metastases, rather than orthotopic tumors. Therefore, the inhibition of tumor metastasis is widely recognized as the key strategy for successful intervention. A cembrane-type diterpene, flaccidoxide-13-acetate, isolated from marine soft coral Sinularia gibberosa, has been reported to have inhibitory effects against RT4 and T24 human bladder cancer invasion and cell migration. In this study, we investigated its suppression effects on tumor growth and metastasis of human HCC, conducting Boyden chamber and Transwell assays using HA22T and HepG2 human HCC cell lines to evaluate invasion and cell migration. We utilized gelatin zymography to determine the enzyme activities of matrix metalloproteinases MMP-2 and MMP-9. We also analyzed the expression levels of MMP-2 and MMP-9. Additionally, assays of tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), the focal adhesion kinase (FAK)/phosphatidylinositide-3 kinases (PI3K)/Akt/mammalian target of the rapamycin (mTOR) signaling pathway, and the epithelial-mesenchymal transition (EMT) process were performed. We observed that flaccidoxide-13-acetate could potentially inhibit HCC cell migration and invasion. We postulated that, by inhibiting the FAK/PI3K/Akt/mTOR signaling pathway, MMP-2 and MMP-9 expressions were suppressed, resulting in HCC cell metastasis. Flaccidoxide-13-acetate was found to inhibit EMT in HA22T and HepG2 HCC cells. Our study results suggested the potential of flaccidoxide-13-acetate as a chemotherapeutic candidate; however, its clinical application for the management of HCC in humans requires further research.

scholarly journals M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jie Yao ◽  
Zefen Wang ◽  
Yong Cheng ◽  
Chao Ma ◽  
Yahua Zhong ◽  
...  
Keyword(s):  
Cell Migration ◽  
Western Blot ◽  
Signaling Pathway ◽  
Target Gene ◽  
Glioma Cells ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
M2 Macrophage ◽  
Mtor Signaling Pathway ◽  
Cell Migration And Invasion

Abstract Background Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. Methods First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays. Results The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway. Conclusion Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway.

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