PTEN expression

Our study defines a new functional role of PRL2 in PTEN regulation through a miR-21-dependent post-transcriptional mechanism, in addition to our previously reported NEDD4-dependent post-translational PTEN regulation. Together, these studies further establish the PRLs as negative regulators of PTEN.

Moreover, expression of these PTEN mutations heightened EGFR activity by sequestering EGFR within endomembranes longer and affected its signaling behavior. Through comprehensive studies on global protein phosphorylation and kinase library analyses in cells with the G36E and L42R PTEN mutations, we identified distinct cancer-promoting pathways activated by EGFR, offering targets for treating GBM with these PTEN alterations.

Neither ERG-positive nor PTEN loss were associated with upgrading during AS. ERG and PTEN biomarkers, despite commonly studied in advanced PCa, have yet no defined role in very low-risk PCa under AS. PI-RADS score was an independent predictor of GS upgrading and extreme upgrading during AS.

Finally, we identify S473-pAKT immunohistochemistry as a useful marker in equivocal cases. In summary, this multi-institutional ring trial illustrates surprisingly heterogeneous outcomes in defining PTEN status by immunohistochemistry.

While HUC-MSC-exo could significantly alleviate the cytotoxicity, apoptosis and inflammatory effects induced by lead on SH-SY5Y cells via partially restoring miR-26a-5p/PTEN pathway. Herein, we conclude that HUC-MSC-exo can alleviate lead-induced toxic effects on SH-SY5Y cells partially through miR-26a-5p/PTEN pathway.

These findings support the potential of rNDV-PTEN as a safe and effective therapy for PDAC with highly activated PI3K/AKT/mTOR signaling caused by KRAS and PTEN gene mutations. Thus, PTEN gene-containing rNDV may be a promising candidate for pancreatic cancer treatment.

Inhibition of SUV39H1 restrains GBM growth and reduces the stem cell properties of GSC. Thus, SUV39H1 might be a prognostic predictor and immunotherapeutic target in patients with GBM.

Animal study results demonstrated that PFKP inhibition curtailed OC tumor growth by modulating PTEN expression. Collectively, these results suggested that lactylation of PFKP at the K392 residue promoted glycolysis in OC cells by regulating PTEN, thereby facilitating the disease's progression.

In addition, all T-LBLs demonstrate constitutive expression of pAKT, indicating the presence of activated AKT signaling, and are sensitive to treatment with the pan-AKT inhibitor MK-2206, suggesting that these lymphomas are dependent on pAKT signaling for their survival. Lastly, ATM-deficiency itself does not cause loss of PTEN or dysregulated AKT signaling, as ATM-deficient non-malignant thymocytes express wild-type levels of PTEN and lack detectable pAKT. This study demonstrates for the first time that the majority of ATM-deficient thymic T-LBLs lose PTEN expression and all depend on AKT signaling for survival, suggesting their potential use as an animal model for PI3K/AKT/MTOR pathway dysfunction in human T-ALL.

The combination of targeted therapy drugs, such as selumetinib and perifosine that inhibit cell signaling pathways involved in cell survival and proliferation, with the expression of tumor suppressor transgenes, such as PTEN, may result in an efficient therapeutic approach against HCC. Moreover, the achieved data revealed that this innovative nanosystem presents a high antitumor effect, demonstrated not only by the enhancement on the programmed cell death, but also by the reduction in cell proliferation capacity. The generated formulation shows a high anticancer effect, demonstrating a high translational potential for future clinical application in HCC treatment.

DICER1MUT and DICER1WT tumors showed different mRNA expression profiles. The FOXL2 mutation is less common in these tumors and is mutually exclusive with the DICER1 mutation.

Demethylation treatment with 5-Aza-dC can inhibit T-ALL cell malignant biological behaviors and enhance the sensitivity to chemotherapy agents possibly, which may be related to the inhibited expressions of DNMT1, DNMT3a, MBD2, and MeCP2, and restored expression activity of PTEN to negatively regulate the PI3K/AKT signal transduction. Our silencing and restoration of PTEN expressions further support our findings, highlighting that demethylation with 5-Aza-dC to restore the anti-tumor activity of the tumor suppressor gene PTEN may be a promising therapeutic option for treating T-ALL.

MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

This upregulation, in turn, enhanced the cells' sensitivity to HER2 antagonists, indicating that DI-1's mechanism involves inhibiting DNMT-1's recruitment to PTEN's promoter region. Consequently, by increasing PTEN expression, DI-1 amplifies the sensitivity of HER2-positive breast cancer cells to treatment, suggesting its potential as a promising therapeutic strategy in this context.

The data indicate that scutellarein is a promising therapeutic agent that inhibits growth, migration, and invasion of CRC cells by down-regulating the expression of AQP 1, 3, and 5 and by PTEN up-regulation, thus inhibiting PI3K/AKT. These molecular alterations represent potential prognostic biomarkers for the metastasis of colon cancer, where the down-regulation of AQPs enhances patient survival.

Magnetic resonance imaging and in vivo imaging analyses confirmed the targeted delivery and efficacy of rNDV-PTEN. These findings highlight the usefulness of rNDV-PTEN as a promising therapeutic agent for GBM, representing a potential advancement in treatment, especially for patients with PTEN deficiency.

In conclusion, the TF KLF9 inhibits the aerobic glycolysis level of breast cancer cells by up-regulating PTEN expression, thereby reducing their resistance to 5-FU. The discovery of this mechanism provides a new theoretical basis for the treatment of breast cancer.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor-suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.

Furthermore, this review explores the expression and regulation of PTEN in different tumor types, as well as its interactions with environmental factors in tumorigenesis. This comprehensive analysis aims to deepen our understanding of the signaling pathways between PTEN and cancer.

In conclusion, this study demonstrated that high CORO1C levels in OC are associated with greater metastasis and worse prognosis. CORO1C negatively regulates PTEN expression, activates the PI3K/AKT pathway, and promotes OC cell malignancy In patients with OC, CORO1C may function as an effective therapeutic and predictive biomarker.

Low PTEN expression (s-score of 6 or less) was used as a diagnostic criterion for high-grade PTs, it showed 100 % sensitivity and 95.2 % specificity in 42 cases of PTs. Currently, PT grading based solely on subjective histologic findings is challenging, but semiquantitative PTEN expression analysis could provide a more accurate and objective way to grade PTs.

Erastin was used to construct ferroptosis induction models...Mechanistically, csi-miR-96-5p and PTEN knockout significantly inhibited ferroptosis through a decrease in ferrous ion (Fe2+) and malondialdehyde (MDA), and an increase in glutathione reductase (GSH), Solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). In conclusion, loss of PTEN promoted the progression of cholangiocarcinoma via the ferroptosis pathway and csi-miR-96-5p delivered by CS-EVs may mediate this process.

Our studies indicate that the CD44/Brg1/PRMT5 regulatory module not only functions to activate positive regulators of pluripotency and self-renewal, but also functions to repress tumor suppressor genes rbl1 and pten. This confers IPF MPCs with the cancer-like property of cell-autonomous self-renewal providing a molecular mechanism for relentless fibrosis progression in IPF.

ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Low PTEN expression is a significant predictor of biochemical recurrence in patients with castration-sensitive PCa who have already undergone prostatectomy.

Our study reveals NPC-associated expression changes of circulating VEGF, PTEN, and SOCS1 mRNAs. These molecular signatures may serve as biomarkers during NPC progression and provide insights into underlying mechanisms. Further validation of their utility as prognostic indicators of NPC is warranted.

This investigation revealed the existence of a circRNA-miRNA-mRNA network in cervical cancer, and preliminary verified the function of circ_0008193-miR-182-5p-PTEN axis in cervical cancer cells, which offers additional guidance on investigating the molecular mechanisms of cervical cancer.

Fifteen miRNAs from 17 studies were found, and together with PTEN expression, they may serve as potential prognostic biomarkers for OSC. High-level levels of miRNA expression are correlated with low PTEN expression, leading to a bad prognosis for OSC.

These findings underscore the importance of PTEN in breast cancer biology and its potential as a therapeutic target. Furthermore these findings confirm the prevalence of advanced stage and aggressive breast cancer tumors in Ghana.

In addition, BM-MSCs significantly increased the protein expression of P53, PTEN, NF-κB, and significantly decreased p-ERK1/2, Raf-1, H-RAS, and TERT. The mentioned effects of IL-2 and IL-4 cytokines released from BM-MSCs on CD34+ LSCs as therapeutic agents were applied by the components of P53, PTEN, NF-κB, p-ERK1/2, Raf-1, and H-RAS signaling pathways.

HQC can improve inflammation and correct the imbalance of uric acid and lipid metabolism in GA rats possibly by inhibiting the PTEN/PI3K/AKT signaling pathway.

Finally, sophocarpine significantly inhibited the growth of tumor both in subcutaneous and orthotopic U251 xenograft GBM model in nude mice via PTEN/PI3K/Akt axis. Taken together, these results suggested that sophocarpine impeded GBM progression via PTEN/PI3K/Akt axis both in vitro and in vivo, providing with a promising therapy for treating GBM.

In contrast, all cases tested positive for cytoplasmic β-catenin. RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

Patients suffering from BRAF mutant melanoma have tumor recurrence within merely 7 months of treatment with a potent BRAF inhibitor (BRAFi) like vemurafenib...Since PTEN plasmid and ARV are distinct in their physicochemical properties, we fabricated PTEN-plasmid loaded lipid nanoparticles (PL-NANO) and ARV-825-loaded nanoliposomes (AL-NANO) to yield a mean particle size of less than 100 nm and greater than 99% encapsulation efficiency for each therapeutic payload...Importantly, simultaneous delivery of PL-NANO and AL-NANO achieved significant upregulation of PTEN expression levels and degradation of BRD4 protein to ultimately downregulate c-Myc levels in BRAFi-resistant melanoma cells. Altogether, lipid nanocarriers delivering this novel lethal cocktail stands as one-of-a-kind gene therapy to target undruggable c-Myc oncogene in BRAFi-resistant melanoma.

Mechanistic investigations revealed that exosomal circ_0004664 functioned as a competitive endogenous RNA for miR-942-5p, resulting in an upregulation of PTEN (P<0.05). Our study highlights the involvement of exosomal circ_0004664 in cell-cell communication during cadmium carcinogenesis, providing a novel insight into the role of exosomal circRNA in this process.

In the syngeneic PC model, IL30-targeting immunoliposomes downregulated NFKB1 expression and prevented intratumoral influx of CD11b+Gr-1+MDCs, Foxp3+Tregs, and NKp46+RORγt+ILC3, and prolonged host survival by inhibiting tumor progression. This study serves as a proof of principle that immunoliposome-based targeted delivery of Cas9gRNA-IL30 represent a potentially safe and effective strategy for PC treatment.

This study suggests that PTEN and p-4E-BP1 might be potential biomarkers for prognostic prediction and therapeutic targets for LARC.

Follow-up was 4-90 months, 2 cases had biochemical recurrence and 1 case died from prostate cancer. The mean age at diagnosis of this group of patients with hereditary prostate cancer was 67.55 years, the mean preoperative PSA was 15.44 ng/ml, and their histomorphology was characterized by a high percentage of intraductal carcinoma and cribriform pattern of the prostate.

These results suggest a model that noncanonical spatial reorganization of phosphoinositides by KRP203 alters the endosomal maturation process, leading to vacuolization. Taken together, this study reveals a previously unrecognized bioactivity of KRP203 as a vacuole-inducing agent and its unique mechanism of phosphoinositide modulation, providing a new insight of phosphoinositide regulation into vacuolization-associated diseases and their molecular pathologies.

In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.

While this study has shed light on some of the functions of ACN, it is important to recognize that natural compounds often interact with multiple molecular targets and engage in intricate signaling cascades. Future research endeavors will concentrate on further elucidating the regulatory mechanisms by which ACN influences PTEN expression, with the goal of enhancing our comprehension and expanding the therapeutic potential of ACN in the treatment of cardiovascular conditions.