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

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.

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

Oncogenesis ◽

10.1038/s41389-021-00304-3 ◽

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.

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lincRNA-RP11400K9.4 Regulates Cell Survival and Migration of Breast Cancer Cells

Cancer Genomics & Proteomics ◽

10.21873/cgp.20231 ◽

2020 ◽

Vol 17 (6) ◽

pp. 769-779

Author(s):

MIGUEL A. FERNÁNDEZ-ROJAS ◽

JORGE MELENDEZ-ZAJGLA ◽

VILMA MALDONADO LAGUNAS

Keyword(s):

Breast Cancer ◽

Cell Survival ◽

Cancer Cells ◽

Breast Cancer Cells ◽

And Migration

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The PI3K/Akt Pathway: Emerging Roles in Skin Homeostasis and a Group of Non-Malignant Skin Disorders

Cells ◽

10.3390/cells10051219 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1219

Author(s):

Yan Teng ◽

Yibin Fan ◽

Jingwen Ma ◽

Wei Lu ◽

Na Liu ◽

...

Keyword(s):

Cell Carcinoma ◽

Akt Pathway ◽

Skin Disorders ◽

Phosphatidylinositol 3 Kinase ◽

Skin Development ◽

Wide Range ◽

Malignant Skin ◽

Solid Foundation ◽

And Migration ◽

Poor Outcomes

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway regulates cell proliferation, differentiation, and migration, along with angiogenesis and metabolism. Additionally, it could mediate skin development and homeostasis. There is much evidence to suggest that dysregulation of PI3K/Akt pathway is frequently associated with several human cutaneous malignancies like malignant melanoma (MM), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (SCC), as well as their poor outcomes. Nevertheless, emerging roles of PI3K/Akt pathway cascade in a group of common non-malignant skin disorders including acne and psoriasis, among others, have been recognized. The enhanced understanding of dysfunction of PI3K/Akt pathway in patients with these non-malignant disorders has offered a solid foundation for the progress of updated therapeutic targets. This article reviews the latest advances in the roles of PI3K/Akt pathway and their targets in the skin homeostasis and progression of a wide range of non-malignant skin disorders and describes the current progress in preclinical and clinical researches on the involvement of PI3K/Akt pathway targeted therapies.

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