Regulation of melanoma cell growth by a miR-21 loaded targeted delivery system based on microparticles and nanoparticles targeting phosphatase and tensin homolog (PTEN)

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.

Differential Immunoexpression of BRAF/V600E, Senescence Markers, PTEN, and T-type Calcium Channels in Acquired Naevi According to their Histopathological and Dermoscopic Classification

BRAF/V600E mutation and other cell growth/growth-control mechanisms are involved in naevogenesis and melanomagenesis. Immunoexpression of BRAF/V600E and other molecules (p16, phosphatase and tensin homologue (PTEN), Ki67, hTERT and Cav3.1 and 3.2 calcium channels) were investigated in 80 histopatho-logically and dermoscopically classified acquired naevi. Regarding BRAF/V600E, dysplastic naevi showed lower immunostaining than common naevi, which was significant in comparison with intradermal naevi, which showed the highest BRAF/V600E histoscore. Junctional naevi showed the lowest BRAF/V600E levels. Globular/cobblestone and reticular dermoscopìc patterns were consistently associated with high and low BRAF/V600E immunoexpression, respectively, but Zalaudek’s peripheral globule pattern (RC/PG) showed the highest BRAF/V600E immunoexpression. Among global patterns, the previously not investigated multicomponent pattern showed the lowest BRAF/V600E immunoexpression. Regarding the remainder biomarkers, this new immunohistochemical features were found, in particular p16 and PTEN low expression in multicomponent pattern; and Ki67, hTERT and Cav.3.1 high expression in CR/PG. In conclusion, histopathology and dermoscopy provide complementary information regarding the biology of melanocytic naevi.

Heparanase-induced proliferation and inhibition of apoptosis are associated with the phosphatase and tensin homologue deleted on chromosome 10/focal adhesion kinase signaling pathway in multiple myeloma

Heparanase (HPSE) has an important effect on the proliferation, invasion, metastasis, and drug resistance of tumor cells. HPSE can promote proliferation and inhibit apoptosis of various solid tumor cells. Previous studies regarding the function of HPSE in multiple myeloma (MM) have primarily focused on tumor invasion and metastasis, whereas few studies have examined the proliferation and apoptosis of MM and the mechanisms associated with HPSE. This study recruited patients with MM and isolated MM cells (RPMI8226, LP-1) were isolated to measure the expression levels of HPSE, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and focal adhesion kinase (FAK) proteins to elucidate their roles in tumor formation. Compared with non-tumor patients, the mRNA and protein expression levels of HPSE and FAK in MM patients increased, whereas the levels of PTEN mRNA and protein decreased. Thus, the increase of HPSE coincided with an increase of FAK and a decrease of PTEN. MM cells exhibiting high HPSE expression exhibited increased proliferation and decreased AS2O3-induced apoptosis. These results indicate that changes in HPSE expression affect the proliferation and apoptosis of MM cells and this mechanism may be associated with the PTEN/FAK signaling pathway. Gene transfection needs proper vector, and proper gene transport system can improve transfection efficiency. In this paper, magnetic nanoparticles were transfected with overexpressed HPSE, and to detect the transfection efficiency and the proliferation ability of MM cells in the control group. The results showed that the cells transfected with magnetic nanoparticles had higher transfection efficiency and higher gene expression level. The results of this experiment provide a new way to explore new cancer therapy genes.

Prognostic value of the PIK3CA, AKT, and PTEN mutations in oral squamous cell carcinoma: literature review

Over 260,000 (2013) new oral squamous cell carcinoma (OSCC) cases are reported annually worldwide. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new molecular markers may be of use in prevention, prognosis, and choice of an appropriate therapy.The intracellular molecular signalling pathway of phosphatidyl-inositol-3-kinase is involved in the process of cell growth, differentiation, migration, and survival. The main components of this pathway: PIK3CA (phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit ), PTEN (phosphatase and tensin homologue deleted on chromosome 10), and AKT (serine-threonine kinase) are potential objects of research when introducing new therapeutic agents. The aim of this paper is to evaluate the PIK3CA, PTEN, and AKT gene mutations as prognostic factors in OSCC and to describe their role in aggressive disease progression. This is crucial for oral cancer biology understanding and for indicating which direction new clinical treatments should take.

The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer

Loss of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which negatively regulates the PI3K–AKT–mTOR pathway, is strongly linked to advanced prostate cancer progression and poor clinical outcome. Accordingly, several therapeutic approaches are currently being explored to combat PTEN-deficient tumors. These include classical inhibition of the PI3K–AKT–mTOR signaling network, as well as new approaches that restore PTEN function, or target PTEN regulation of chromosome stability, DNA damage repair and the tumor microenvironment. While targeting PTEN-deficient prostate cancer remains a clinical challenge, new advances in the field of precision medicine indicate that PTEN loss provides a valuable biomarker to stratify prostate cancer patients for treatments, which may improve overall outcome. Here, we discuss the clinical implications of PTEN loss in the management of prostate cancer and review recent therapeutic advances in targeting PTEN-deficient prostate cancer. Deepening our understanding of how PTEN loss contributes to prostate cancer growth and therapeutic resistance will inform the design of future clinical studies and precision-medicine strategies that will ultimately improve patient care.

Mechanism of PRL2 phosphatase-mediated PTEN degradation and tumorigenesis

Tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) levels are frequently found reduced in human cancers, but how PTEN is down-regulated is not fully understood. In addition, although a compelling connection exists between PRL (phosphatase of regenerating liver) 2 and cancer, how this phosphatase induces oncogenesis has been an enigma. Here, we discovered that PRL2 ablation inhibits PTEN heterozygosity-induced tumorigenesis. PRL2 deficiency elevates PTEN and attenuates AKT signaling, leading to decreased proliferation and increased apoptosis in tumors. We also found that high PRL2 expression is correlated with low PTEN level with reduced overall patient survival. Mechanistically, we identified PTEN as a putative PRL2 substrate and demonstrated that PRL2 down-regulates PTEN by dephosphorylating PTEN at Y336, thereby augmenting NEDD4-mediated PTEN ubiquitination and proteasomal degradation. Given the strong cancer susceptibility to subtle reductions in PTEN, the ability of PRL2 to down-regulate PTEN provides a biochemical basis for its oncogenic propensity. The results also suggest that pharmacological targeting of PRL2 could provide a novel therapeutic strategy to restore PTEN, thereby obliterating PTEN deficiency-induced malignancies.

Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer

Long non-coding RNAs (lncRNAs) are emerging as regulators in cancer development and progression, and aberrant lncRNA profiles have been reported in several cancers. Here, we evaluated the potential of using the maternally expressed gene 3 (MEG3) tissue level as a prognostic marker in high-grade serous ovarian cancer (HGSOC), the most common and deadliest gynecologic malignancy. To the aim of the study, we measured MEG3 transcript levels in 90 pre-treatment peritoneal biopsies. We also investigated MEG3 function in ovarian cancer biology. We found that high MEG3 expression was independently associated with better progression-free (p = 0.002) and overall survival (p = 0.01). In vitro and in vivo preclinical studies supported a role for MEG3 as a tumor suppressor in HGSOC, possibly through modulation of the phosphatase and tensin homologue (PTEN) network. Overall, results from this study demonstrated that decreased MEG3 is a hallmark for malignancy and tumor progression in HGSOC.