MicroRNAs are negative regulators of mRNA, and latest studies show that "mRNAs can also inhibit microRNAs". With these reciprocal interactions, different mRNAs with identical "microRNA binding site" cim regulate each other by competitively binding to the same microRNA pool. This is the novel competing endogenous RNA (ceRN A)regulating mechanism. The ceRN A mechanism, which is a totally new regulating mechanism , greatly expands the regulatory network across genes. It has been proved by experimental evidence that, in HCT116 colon cancer cells,KRAS and PTEN , ZEB2 and PTEN can regulate each other by ceRNA mechanism.
Colorectal Neoplasms ; genetics ; HCT116 Cells ; Humans ; MicroRNAs ; genetics ; PTEN Phosphohydrolase ; RNA, Messenger

The present study was aimed to investigate the expression of tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) in mouse endometrium during early pregnancy and its possible role during blastocyst implantation. Real-time fluorescent quantitative PCR (FQ-PCR) and immunohistochemical techniques were applied to detect PTEN mRNA and protein expressions in endometrium in un-pregnant and pregnant mice on days 1, 3, 4, 5, 7 of pregnancy, respectively. In addition, PTEN antisense oligonucleotide was injected into the horns of uterus in pregnant mice on day 3 of pregnancy and its effects on blastocyst implantation was detected in vivo. The higher expressions of PTEN mRNA and protein were observed in pregnant mice compared with that in un-pregnant mice, with a steady increasing from day 1 to 7 and reaching the maximal level on day 5 of pregnancy. PTEN antisense oligonucleotide decreased the number of implanted blastocysts compared with saline. The results suggest that PTEN might associate with apoptosis of luminal epithelial and decidual cells, coordinating decidualization of endometrium and invasion of trophoblastic cells. Thus, PTEN may participate in the process of blastocyst implantation in mice.
Animals ; Chromosomes ; Embryo Implantation ; Endometrium ; metabolism ; Female ; Mice ; PTEN Phosphohydrolase ; metabolism ; Pregnancy ; Trophoblasts ; metabolism

Child ; Codon, Nonsense ; Female ; Hamartoma Syndrome, Multiple ; diagnosis ; genetics ; Humans ; PTEN Phosphohydrolase ; genetics

Pten gene is the first antioncogene with dual phosphatase activity discovered so far, pten gene regulates the cell cycle progress, apoptosis, metastasis and invasion of the tumor cells through negatively regulating the multiple signaling transduction pathways. Multiple myeloma (MM) is a malignant tumor occurring in terminal stage of B cell differentiation. The genetic changes are considered as the important factors in MM pathogenesis, among which the deletion of antioncogene is a critical genetic change. However, little is known about the genetic change of pten in MM. This review summarizes the research advance on pten in MM including structure of pten, mechanism of pten effect and correlation of pten with MM in order to provide some references for the investigating new gene target to treat the MM.
Humans ; Multiple Myeloma ; metabolism ; therapy ; PTEN Phosphohydrolase ; genetics ; metabolism ; Signal Transduction

OBJECTIVETo explore the mechanism of PTEN gene expression silence in leukemia cells, and the effect of induced PTEN gene expression in leukemia cells.

METHODSMethylation status of PTEN in leukemic cell lines, including HL-60, Nalm-6, NB4, U937, Raji, K562 and KG-1a was assessed by methylation specific PCR (MSP). The cell lines were then treated with different concentrations of methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR). After that the changes in PTEN methylation status were detected by MSP, and PTEN mRNA expression level by reverse transcription PCR (RT-PCR). Growth inhibition and apoptosis of HL-60 and Nalm-6 cells induced by 5-Aza-CdR were observed by MTT assay, and Wright and Annexin V staining, respectively.

RESULTSHypermethylation of PTEN promoter was detected in HL-60, U937, Nalm-6, Raji and KG-1a, while hypomethylation was found in NB4 and K562 by MSP. After 5-Aza-CdR treatment, the hypermethylation status of PTEN promoter in HL-60 and Nalm-6 cells was reversed and their PTEN mRNA expression levels were up regulated in dose dependent manner with the 5-Aza-CdR concentrations, and the cell apoptosis was induced.

CONCLUSIONHypermethylation in the promoter region is one of major mechanisms responsible for transcriptional suppression of PTEN. Methyltransferase inhibitor could induce the expression of PTEN gene and lead to the leukemia cells apoptosis.

This study was aimed to explore the effects of oleanolic acid on PTEN expression and apoptosis of Jurkat cells. The inhibitory rate was measured by Cell Counting Kit-8. The apoptotic nucleus morphous was observed by Hoechst 33258 staining. The apoptosis rate of Jurkat cells were determined by flow cytometry with Annexin V/PI double staining. PTEN mRNA and protein were detected by quantitative real-time PCR and Western blot respectively. The results showed that oleanolic acid inhibited the proliferation of Jurkat cells in time- and dose-dependent manners. The 50% growth inhibition (IC(50)) at 12, 24 and 48 hours were about 85.35 µmol/L, 53.66 µmol/L and 33.18 µmol/L respectively. Flow cytometric assay showed that the apoptotic rates of Jurkat cells treated with oleanolic acid (0, 40, 80 and 160 µmol/L) for 24 hours were 6.72%, 19.8%, 28.72% and 30.12% (p < 0.05). PTEN mRNA and protein expressions were up-regulated in Jurkat cells treated with oleanolic acid of concentration 80 µmol/L and 160 µmol/L for 24 hours. It is concluded that up-regulation of PTEN mRNA and PTEN protein may be involved in oleanolic acid-induced Jurkat cell apoptosis.
Apoptosis ; drug effects ; Cell Proliferation ; Humans ; Jurkat Cells ; Oleanolic Acid ; pharmacology ; PTEN Phosphohydrolase ; metabolism ; Up-Regulation

This study was aimed to investigate whether endothelium-specific deletion of PTEN can affect hemangioblast development in the AGM region of mouse embryos. Based on Cre/loxP system, the Tie2CrePten(loxp/loxp) and Tie2CrePten(loxp/wt) mouse embryos were obtained. The genotype was identified by PCR. After treated with type I collagenase, the AGM region was dispersed into single-cell suspension, and then was cultured in blast colony-forming cell (BL-CFC) media. The number of BL-CFC was counted 4 or 5 days later. The hematopoietic capacity of BL-CFC was detected in methylcellulose culture system and the endothelial potential was assessed by tube-like structure formation on Matrigel. The results showed that the number of BL-CFC in AGM region of Tie2CrePten(loxp/loxp) mouse embryo decreased as compared with Tie2CrePten(loxp/wt) embryo. Whereas the hematopoietic capacity of mutant BL-CFC was enhanced, the endothelial potential, as evaluated by tube-like structure formation in vitro, was significantly reduced. It is concluded that the endothelial PTEN is capable of exerting regulatory functions on both the numbers and the dual potential of hemangioblast in mouse AGM region.
Animals ; Cell Differentiation ; Cells, Cultured ; Hemangioblasts ; Hematopoietic Stem Cells ; cytology ; Mice ; PTEN Phosphohydrolase ; genetics

OBJECTIVETo explore expression and significance of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and survivin in acute lymphoblastic leukemia (ALL).

METHODSPeripheral blood samples were collected from 68 patients with ALL in our hospital including 48 newby diagnosed patients, 13 patients in remission, 7 patients in relapse, and 20 healthy volunteers (control). The expressions of PTEN and survivin mRNA and protein were detected by real time PCR, Western blot and respectively, and clinical pathological parameter was analyzed.

RESULTSThe expressions of PTEN mRNA and protein in newby diagnosed, remission and relapsed group were lower than that in control group (P<0.01). The expressions of PTEN mRNA and protein in newly diagnosed and relapsed groups were lower than that in remission group (P<0.01). The expressions of survivin mRNA and protein in newly diagnosed, remission and relapsed group were higher than that in control group (P < 0.01). The expressions of survivin mRNA and protein in newly diagno sed and relapsed groups were higher than that in remission group (P < 0.01). The expressions of PTEN and survivin mRNA did not relahed with the age, sex and white blood count in ALL patients, and also did not related with the morphological classification in newly diagnosed ALL (P>0.05), but related with immunological calssification in newly diagnosed ALL (P < 0.01). The expressions of PTEN and survivin were negatively correlated in ALL (P < 0.01).

CONCLUSIONPTEN and survivin play an important role in the occurrence, development and prognosis in ALL, and may be one of the potential targets for ALL treatment.

This study explored the effects of resveratrol(Res) on the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) and the fibrosis of rat renal tubular epithelial cells in a high-glucose environment and the possible mechanism underlying the fibrosis reduction. After the pretreatment of rat renal tubular epithelial cells(NRK-52 E) cultured in a high-glucose condition with Res or PTEN inhibitor SF1670, they were divided into several groups, i.e., normal glucose(NG), normal glucose + SF1670(NS), high glucose(HG), high glucose + SF1670(HS), high glucose + Res at different concentrations(5, 10, 25 μmol·L~(-1)). The expression and distribution of E-cadherin and α-SMA in renal tubular epithelial cells were observed by immunofluorescence cytochemistry. The protein expression levels of PTEN, E-cadherin, α-SMA, p-Akt~((Thr308)) and collagen Ⅳ were determined by Western blot. Real-time PCR was employed to detect the expression of PTEN mRNA. Compared with the NG group, the HG group witnessed the reduced expression of PTEN mRNA, PTEN protein and E-cadherin protein, but saw the increased expression of α-SMA, p-Akt~((Thr308)) and collagen Ⅳ proteins. Besides, with the increase in Res concentration, the expression levels of PTEN mRNA, PTEN protein and E-cadherin protein gradually increased, while those of α-SMA, collagen Ⅳ, p-Akt~((Thr308)) proteins gradually decreased in the Res groups, showing a dose-effect dependence, compared with the HG group. No distinct difference was found between the NS group and the NG group. The expression level of E-cadherin was even lower and those of α-SMA, p-Akt~((Thr308)), and collagen Ⅳ were higher in the HS group than in the HG group, with no marked difference shown in the two groups in terms of PTEN mRNA and protein. Although the PTEN inhibitor did not affect PTEN, the expression changes of the other proteins were opposite to the results after Res treatment and the fibrosis was aggravated, which suggested that SF1670 promoted the fibrosis by inhibiting PTEN, activating Akt and increasing the synthesis of collagen Ⅳ and other extracellular matrix. The results show that Res can antagonize the high glucose-mediated fibrosis of renal tubular epithelial cells. This may be achieved via the up-regulation of PTEN and the inhibition of PI3 K/Akt signaling pathway.
Animals ; Epithelial Cells ; Fibrosis ; Glucose ; PTEN Phosphohydrolase/genetics* ; Rats ; Resveratrol/pharmacology*

OBJECTIVE: To investigate the relationship of PTEN/PI3K/AKT signaling pathway protein expression with apoptosis and drug-resistance of children's ALL primary cells treated with daunorubicin (DNR). METHODS: The bone marrow mononuclear cells in newly diagnosed and untreated B-ALL children were collected and cultured. After the treatment of primary-cultured cells with DNR of final concentration 0.5 mg/L for 24 h, the cell apoptosis rate was detected by using cell apoptosis assay kit; the samples were collected at the on test of culture and after drug treatment, then expression levels of PTEN, PI3K and AKT proteins were detected by Western blot, moreover the interindex correlation was analyzed. RESULTS: After DNR treatment, the apoptosis rate in PTEN low expression group was lower than that in PTEN high expression group (P＜0.05), showing high positive correlation of the cell apoptosis rate with the expression of PTEN before DNR treatment; the cell apoptosis rate in PI3K and AKT low expression group was higher than that in PI3K and AKT high expression group (P＜0.01); however, the expression of PI3K and AKT proteins was down-regulated after treatment with DNR (P＜0.01). CONCLUSION The difference of PTEN expression is present in primary cells of B-ALL children, however the change of PTEN expression is not significant after DNR treatment, suggesting that the PTEN expression correlates with DNR-resistance. The DNR can induce the apoptosis of childrens B-ALL primary cells by down-regulating the expression of PI3K and AKT signaling pathway proteins.
Apoptosis ; Child ; Daunorubicin ; Humans ; PTEN Phosphohydrolase ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Signal Transduction