Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy

The modulatory effect of miR-21 on the proliferation of melanoma cells through stimulation of PTEN (Phosphatase and tensin homologue deleted on chromosome 10) expression was investigated in the current study. PTEN, as a tumor suppressor, is expressed in low levels in melanoma tissues and cell lines. Nevertheless, miR-21 can stimulate cancer development and suppress cell apoptosis. Overexpression of PTEN substantially impaired the proliferation of miR-21-treated melanoma cells. In addition, miR-21 and PTEN were observed to exhibit a combinatorial effect, whereas miR-21 could negatively regulate the expression of PTEN. In conclusion, these findings demonstrate that miR-21 affects melanoma development by targeting PTEN, establishing a new strategy for treating malignant melanoma. Furthermore, in this study, microparticles and nanoparticles were employed as carriers to construct, through the self-assembly method, nanocapsules carrying miR-21 in order to develop an efficient nanocapsule delivery system of miR-21 against melanoma cells.

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PTEN, A Target of Microrna-374b, Contributes to the Radiosensitivity of Canine Oral Melanoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20184631 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4631 ◽

Cited By ~ 3

Author(s):

Shunsuke Noguchi ◽

Ryo Ogusu ◽

Yusuke Wada ◽

Satoshi Matsuyama ◽

Takashi Mori

Keyword(s):

Radiation Therapy ◽

Luciferase Activity ◽

Melanoma Cells ◽

Expression Level ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

Oral Melanoma ◽

Luciferase Activity Assay ◽

Oral Malignant Melanoma ◽

Pre Treatment

Canine oral malignant melanoma (CoMM) is often treated by radiation therapy in veterinary medicine. However, not all cases are successfully managed by this treatment. For improved efficacy of radiation therapy, biomarkers predicting the radiosensitivity of melanoma cells need to be explored. Here, we, first, developed the radioresistant CoMM cell line, KMeC/R. We found that the expression level of phosphatase and tensin homolog (PTEN) of KMeC/R cells was significantly downregulated compared with KMeC cells. Overexpression of PTEN successfully restored the radiosensitivity of KMeC/R cells, and silencing of PTEN significantly increased the radioresistance of the CoMM cells tested. Next, we focused on microRNAs (miRNAs) to explore the mechanisms of downregulation of PTEN in KMeC/R cells. miR-374b was upregulated in KMeC/R cells compared with that in KMeC cells and in the irradiated CoMM cells tested. Furthermore, miR-374b directly targeted PTEN based on the luciferase activity assay. Moreover, the extrinsic miR-374b significantly increased the radioresistance of KMeC cells. In addition, the expression level of PTEN was significantly downregulated and that of miR-374b tended to be upregulated in recurrent CoMM tissues after radiation therapy compared with the pre-treatment tissues. Thus, the current study suggested that the miR-374b/PTEN signaling pathway possibly plays an important role in CoMM radiosensitivity.

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Chamazulene-Rich Artemisia arborescens Essential Oils Affect the Cell Growth of Human Melanoma Cells

Plants ◽

10.3390/plants9081000 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1000

Author(s):

Alessandra Russo ◽

Maurizio Bruno ◽

Rosanna Avola ◽

Venera Cardile ◽

Daniela Rigano

Keyword(s):

Essential Oils ◽

Defense Mechanisms ◽

Membrane Integrity ◽

Melanoma Cells ◽

Human Malignant Melanoma ◽

Phosphatase And Tensin Homolog ◽

Cell Membrane Integrity ◽

Melanoma Cancer ◽

Tensin Homolog ◽

Ic50 Values

Artemisia arborescens is an aromatic shrub whose essential oils are considered a potential source of molecules with industrial and pharmaceutical interest. The chemical profile of A. arborescens essential oils (EOs) was shown to be quite variable and various chemotypes have been identified. In this study, we compared the EOs composition of A. arborescens leaves and flowers collected from four different locations in Sicily. The EOs were assayed for their antiproliferative activity against A375 human malignant melanoma cells, also testing cell viability and cell membrane integrity. The evaluation of DNA fragmentation and caspase-3 activity assay was employed for the detection of apoptosis. The expression of Bcl-2, Bax, cleaved caspase-9, PTEN (Phosphatase and tensin homolog), Hsp70 (Heat Shock Protein 70 kilodaltons) and SOD (superoxide dismutase) proteins was evaluated by Western blot analysis. The levels of ROS and GSH were also analyzed. Results show that EOs presented significant differences in their composition, yield, and cytotoxic activity depending on the collection site. The chamazulene/camphor-rich EOs from plants collected in Acqua Calda (Lipari) resulted particularly active on melanoma cancer cells (IC50 values of 6.7 and 4.5 µg/mL), being able to trigger apoptotic death probably interfering with endogenous defense mechanisms. These oils may be considered as a natural resource of chamazulene, containing this compound up to 63%.

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High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN (Phosphatase and Tensin Homolog)

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314458 ◽

2020 ◽

Vol 40 (8) ◽

pp. 1854-1869

Author(s):

Keith A. Strand ◽

Sizhao Lu ◽

Marie F. Mutryn ◽

Linfeng Li ◽

Qiong Zhou ◽

...

Keyword(s):

Protein Expression ◽

High Throughput ◽

Knockout Mice ◽

Vascular Remodeling ◽

Dna Methyltransferase ◽

Dna Methyltransferase 1 ◽

Protective Effects ◽

High Throughput Screen ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog

Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation. Conclusions: Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.

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miR-139-5p promotes neovascularization in diabetic retinopathy by regulating the phosphatase and tensin homolog

Archives of Pharmacal Research ◽

10.1007/s12272-021-01308-8 ◽

2021 ◽

Vol 44 (2) ◽

pp. 205-218

Author(s):

Zhongwei Zhang ◽

Caiping Song ◽

Tao Wang ◽

Lei Sun ◽

Ling Qin ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog

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The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22041525 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1525

Author(s):

Chunling Huang ◽

Ji Bian ◽

Qinghua Cao ◽

Xin-Ming Chen ◽

Carol A. Pollock

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Kidney Diseases ◽

Mitochondrial Protein ◽

Physiological Role ◽

Close Link ◽

Promising Alternative ◽

Diabetic Kidney ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog

Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.

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Hepatic HuR protects against the pathogenesis of non-alcoholic fatty liver disease by targeting PTEN

Cell Death and Disease ◽

10.1038/s41419-021-03514-0 ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Mi Tian ◽

Jingjing Wang ◽

Shangming Liu ◽

Xinyun Li ◽

Jingyuan Li ◽

...

Keyword(s):

Glucose Metabolism ◽

Hepatic Steatosis ◽

Chow Diet ◽

Alcoholic Fatty Liver ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

Pten Mrna ◽

Normal Chow ◽

Mice Liver

AbstractThe liver plays an important role in lipid and glucose metabolism. Here, we show the role of human antigen R (HuR), an RNA regulator protein, in hepatocyte steatosis and glucose metabolism. We investigated the level of HuR in the liver of mice fed a normal chow diet (NCD) and a high-fat diet (HFD). HuR was downregulated in the livers of HFD-fed mice. Liver-specific HuR knockout (HuRLKO) mice showed exacerbated HFD-induced hepatic steatosis along with enhanced glucose tolerance as compared with control mice. Mechanistically, HuR could bind to the adenylate uridylate-rich elements of phosphatase and tensin homolog deleted on the chromosome 10 (PTEN) mRNA 3′ untranslated region, resulting in the increased stability of Pten mRNA; genetic knockdown of HuR decreased the expression of PTEN. Finally, lentiviral overexpression of PTEN alleviated the development of hepatic steatosis in HuRLKO mice in vivo. Overall, HuR regulates lipid and glucose metabolism by targeting PTEN.

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An Immunohistochemical Study of the PTEN/AKT Pathway Involvement in Canine and Feline Mammary Tumors

Animals ◽

10.3390/ani11020365 ◽

2021 ◽

Vol 11 (2) ◽

pp. 365

Author(s):

Pietro Asproni ◽

Francesca Millanta ◽

Lorenzo Ressel ◽

Fabio Podestà ◽

Francesca Parisi ◽

...

Keyword(s):

Immunohistochemical Study ◽

Lymphatic Invasion ◽

Pten Expression ◽

Akt Pathway ◽

Phosphatase And Tensin Homolog ◽

Mammary Carcinomas ◽

Tensin Homolog ◽

Aggressive Tumors ◽

Aggressive Subtype ◽

Viral Oncogene Homolog

Phosphatase and tensin homolog deleted on chromosome10 (PTEN), phospho-v-Akt murine thymoma viral oncogene homolog (AKT), and the Rapamycin-Insensitive Companion of mTOR (Rictor) expression was investigated by immunohistochemistry in 10 canine mammary adenomas (CMAs), 40 canine mammary carcinomas (CMCs), and 30 feline mammary carcinomas (FMCs). All the CMAs, 25 of 40 CMCs (63%) and 7 of 30 FMCs (23%), were PTEN-positive. In dogs, no CMAs and 15 of 25 CMCs (37%) expressed phospho-AKT (p-AKT), while 24 of 30 FMCs (82%) were p-AKT-positive. One of 10 CMAs (10%), 24 of 40 CMCs (60%) and 20 of 30 FMCs (67%) were Rictor-positive. In the dog, PTEN expression correlated with less aggressive tumors, absence of lymphatic invasion, and longer survival. P-AKT expression correlated with more aggressive subtype, lymphatic invasion, and poorer survival and Rictor expression with lymphatic invasion. In cats, PTEN correlated with less aggressive carcinomas, absence of lymphatic invasion, and better survival. P-AKT and Rictor expression correlated with poorer survival. PTEN expression was inversely correlated with p-AKT and Rictor in both species, while p-AKT positively correlated with Rictor expression. A strong PTEN/AKT pathway involvement in behavior worsening of CMT and FMTs is demonstrated, providing a rationale for further studies of this pathway in veterinary oncology.

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Esthetic and Functional Improvement of Asymmetric Lower Limb Overgrowth in a Proteus Syndrome Patient: a Combined Surgical Technique

Indian Journal of Surgery ◽

10.1007/s12262-021-02773-7 ◽

2021 ◽

Author(s):

Francesca Riccardi ◽

Simone Catapano ◽

Giuseppe Cottone ◽

Dino Zilio ◽

Luca Vaienti

Keyword(s):

Adipose Tissue ◽

Lower Limb ◽

Vascular Malformations ◽

Functional Improvement ◽

Proteus Syndrome ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

Genetic Mosaicism ◽

Phosphoinositide 3 Kinase ◽

The Right

AbstractProteus syndrome is a rare, sporadic, congenital syndrome that causes asymmetric and disproportionate overgrowth of limbs, connective tissue nevi, epidermal nevi, alteration of adipose tissue, and vascular malformations. Genetic mosaicism, such as activating mutations involving protein kinase AKT1, phosphoinositide 3 kinase (PI3-K), and phosphatase and tensin homolog (PTEN), may be important causes of Proteus syndrome. However, many patients have no evidence of mutations in these genes. Currently, the diagnosis is clinical and based on phenotypic features. This article reports a case of Proteus syndrome in a 14-year-old female patient who presented with linear epidermal nevi, viscera anomalies, and adipose tissue dysregulation. She showed an asymmetric progressive overgrowth of the right lower limb after birth bringing relevant functional and esthetic consequences. Therefore, she asked a plastic surgery consultation and a surgical treatment with a combined technique was planned. With our approach, we were able to reduce leg diameter and improve joint mobility reliably and safely with satisfying esthetic results.

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