scholarly journals miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities

Oncogenesis ◽  
2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Xinzhi Yang ◽  
Jiangang Liu ◽  
Chenci Wang ◽  
Kenneth King-yip Cheng ◽  
Hongchao Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Tumor Growth ◽  
Cell Survival ◽  
Akt Pathway ◽  
Therapeutic Approaches ◽  
Functional Roles ◽  
Human Gbm ◽  
And Migration ◽  
Hydroxyeicosatetraenoic Acids ◽  
Novel Therapeutic

AbstractThe development of glioblastoma (GBM) is typically accompanied by marked changes in lipid metabolism. Oxylipins and their catalyzed enzymes lipoxygenases (LOXs) have been shown to participate in the development of cancers via multiple pathways, while the understanding of LOXs in GBM remains enigmatic. Thus, we aimed to explore the expression and functional roles of LOXs in the development of GBM. Here we showed that ALOXE3 was markedly down-regulated in human GBM. Knockdown of ALOXE3 in GBM cells fostered the orthotopic tumor growth and shortened lifespan in mice. ALOXE3 deficiency rendered GBM cells resistant to p53-SLC7A11 dependent ferroptosis, promoting GBM cell survival. Mechanistically, miR-18a directly targeted ALOXE3 and suppressed its expression and functions in GBM cells. Furthermore, ALOXE3 silencing promoted 12-hydroxyeicosatetraenoic acids (12-HETE) secretion from GBM cells, in turn, 12-HETE enhanced migration of GBM cells by activating Gs-protein-coupled receptor (GsPCR)-PI3K-Akt pathway in an autocrine manner. Altogether, miR-18a/ALOXE3 axis exerts tumor promoting functions by regulating ferroptosis and migration of GBM cells. Targeting miR-18a/ALOXE3 axis may provide novel therapeutic approaches for GBM treatment.

scholarly journals Targetting an LncRNA P5848-ENO1 axis inhibits tumor growth in hepatocellular carcinoma

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Xidan Zhu ◽  
Hui Yu ◽  
Baolin Li ◽  
Jing Quan ◽  
Zhangrui Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Cell Growth ◽  
Tumor Growth ◽  
Cell Survival ◽  
Cancer Cell ◽  
Expression Level ◽  
High Recurrence Rate ◽  
Gene And Protein Expression ◽  
And Migration

Abstract Hepatocellular carcinoma (HCC) has a high recurrence rate and poor clinical outcome after currently used therapies, including radiofrequency ablation. To explore the possible mechanisms for the relapse of HCC, in the present study we focussed on long non-coding RNA (LncRNA), which has been reported to be involved in tumorigenesis. We identified an LncRNA P5848, whose expression level was up-regulated in tumor samples from HCC patients after radiofrequency ablation. As such, we speculated that LncRNA P5848 may play a role in tumor growth. Here we showed that LncRNA P5848, whose up-regulation can lead to HCC cancer cell proliferation and migration. In vitro and in vivo overexpression of LncRNA P5848 promoted cell growth, cell survival, and cell invasion, whereas LncRNA P5848 depletion exerts opposite effects. Mechanistically, we have found that ENO1 was the target of LncRNA P5848. LncRNA P5848 up-regulated the gene and protein expression level of ENO1, promoting tumor growth and cell survival. However, siRNA-mediated knockdown of ENO1 counteracted the effects of LncRNA P5848 on cancer cell growth, cell survival, and migration. Taken together, LncRNA P5848 promotes HCC development by up-regulating ENO1, indicating that LncRNA P5848-ENO1 axis is a potential therapeutic target for the treatment of HCC.

Upregulation of DJ-1 expression in melanoma regulates PTEN/AKT pathway for cell survival and migration

2020 ◽  
Author(s):  
Yoon Jin Lee ◽  
Woo Il Kim ◽  
Tae Heum Park ◽  
Jin Ho Bae ◽  
Hae Seon Nam ◽  
...  
Keyword(s):  
Cell Survival ◽  
Akt Pathway ◽  
And Migration

scholarly journals MICAL2 Promotes Proliferation and Migration of Glioblastoma Cells Through TGF-β/p-Smad2/EMT-Like Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Bei Pu ◽  
Xu Zhang ◽  
Tengfeng Yan ◽  
Yuntao Li ◽  
Baohui Liu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Signaling Pathway ◽  
Type I ◽  
Glioblastoma Cells ◽  
Cycle Arrest ◽  
Tumor Growth Factor ◽  
Promising Therapeutic Target ◽  
Human Gbm ◽  
And Migration ◽  
Proliferation And Migration

Recent studies showed that molecule interacting with CasL2 (MICAL2) could be a novel tumor growth factor, and it is closely associated with tumor growth and invasion. However, the role it plays in glioblastoma (GBM) and its potential mechanisms are currently unknown. Our study is designed to identify the effect of MICAL2 on GBM cells and the potential mechanisms behind it. Here, we found that MICAL2 interacts with TGF receptor-type I (TGFRI) and promotes the proliferation and migration of glioblastoma through the TGF-β/p-Smad2/EMT-like signaling pathway. MICAL2-knockdown inhibited the proliferation of glioblastoma cells, which was related to cell cycle arrest and downregulation of DNA replication. The invasion abilities of U87 and U251 cells were reduced after the knockdown of MICAL2. MICAL2 promoted the growth of GBM in nude mice. High MICAL2 predicts poor outcome of GBM patients. MICAL2 could be identified as a novel promising therapeutic target for human GBM.

scholarly journals Recent Progress on Lipid Intake and Chronic Kidney Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Ke Pei ◽  
Ting Gui ◽  
Chao Li ◽  
Qian Zhang ◽  
Huichao Feng ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Lipid Metabolism ◽  
Kidney Disease ◽  
Recent Progress ◽  
Lipid Uptake ◽  
Vicious Cycle ◽  
Therapeutic Approaches ◽  
Lipid Abnormalities ◽  
Novel Therapeutic

The incidence of chronic kidney disease (CKD) is associated with major abnormalities in circulating lipoproteins and renal lipid metabolism. This article elaborates on the mechanisms of CKD and lipid uptake abnormalities. The viewpoint we supported is that lipid abnormalities directly cause CKD, resulting in forming a vicious cycle. On the theoretical and experiment fronts, this inference has been verified by elaborately elucidating the role of lipid intake and accumulation as well as their influences on CKD. Taken together, these findings suggest that further understanding of lipid metabolism in CKD may lead to novel therapeutic approaches.

scholarly journals Overexpression of Long Noncoding RNA PTENP1 Inhibits Cell Proliferation and Migration via Suppression of miR-19b in Breast Cancer Cells

2018 ◽  
Vol 26 (6) ◽  
pp. 869-878 ◽  
Author(s):  
Xianbiao Shi ◽  
Xiaoqiao Tang ◽  
Lei Su
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cell Lines ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Negative Role ◽  
And Migration ◽  
Increase Cell Survival

This study aimed to investigate the effect of long noncoding RNA PTENP1 in the development of breast cancer (BC). Quantitative real-time PCR was utilized to determine the expression of PTENP1 in tissues and cell lines. pcDNA3.1 and shRNA were used to over- and low-express PTENP1 in BC cell lines, and miR-19b mimic and inhibitor were utilized to over- and low-express miR-19b. Then the abilities of cell survival, apoptosis, migration, and invasion were assessed in BC cells with different expression levels of PTENP1 and miR-19b. The expression of PTENP1 was significantly downregulated in both BC tissues and cell lines. Overexpressed PTENP1 could significantly increase cell survival, colony forming, migration, and invasion but decrease apoptosis in BC cell lines. However, overexpressed miR-19b performed contrary effects compared with PTENP1 on cell survival, colony forming, migration, invasion, and apoptosis in BC cell lines. miR-19b can be downregulated by PTENP1, and the effect of overexpressed PTENP1 on the PI3k/Akt pathway could be aborted by overexpressed miR-19b. PTENP1 performed a negative role in the development of BC via downregulating miR-19 probably through the PTEN/PI3K/Akt pathway.

scholarly journals Tumor Decelerating and Chemo-Potentiating Action of Methyl Jasmonate on a T Cell Lymphoma In Vivo: Role of Altered Regulation of Metabolism, Cell Survival, Drug Resistance, and Intratumoral Blood Flow

2021 ◽  
Vol 11 ◽  
Author(s):  
Yugal Goel ◽  
Saveg Yadav ◽  
Shrish Kumar Pandey ◽  
Mithlesh Kumar Temre ◽  
Babu Nandan Maurya ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Lipid Metabolism ◽  
Tumor Growth ◽  
Cell Survival ◽  
Methyl Jasmonate ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Ph Homeostasis

Methyl jasmonate (MJ), a natural oxylipin, possesses a broad spectrum of antineoplastic potential in vitro. However, its tumor growth impeding and chemo-potentiating action has not been adequately investigated in vivo. Using a murine thymus-derived tumor named Dalton’s Lymphoma (DL), in the present study, we examined if intra-tumoral administration of MJ can cause tumor growth impedance. We also explored the associated molecular mechanisms governing cell survival, carbohydrate & lipid metabolism, chemo-potentiation, and angiogenesis. MJ administration to tumor-transplanted mice caused deceleration of tumor growth accompanying prolonged survival of the tumor-bearing mice. MJ-dependent tumor growth retardation was associated with the declined blood supply in tumor milieu, cell cycle arrest, augmented induction of apoptosis and necrosis, deregulated glucose and lipid metabolism, enhanced membrane fragility of tumor cells, and altered cytokine repertoire in the tumor microenvironment. MJ administration modulated molecular network implicating Hsp70, Bcl-2, TERT, p53, Cyt c, BAX, GLUT-1, HK 2, LDH A, PDK-1, HIF-1α, ROS, MCT-1, FASN, ACSS2, SREBP1c, VEGF, cytokine repertoire, and MDR1, involved in the regulation of cell survival, carbohydrate and fatty acid metabolism, pH homeostasis, and drug resistance. Thus, the present study unveils novel molecular mechanisms of the tumor growth decelerating action of MJ. Besides, this preclinical study also establishes the adjunct therapeutic potential of MJ. Hence, the present investigation will help to design novel anti-cancer therapeutic regimens for the treatment of hematological malignancies.

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