Effect of adenovirus-mediated PTEN gene on ulcerative colitis-associated colorectal cancer

Li, Zhi; Liu, Gong Xiang; Liu, Yu Lan; Chen, Xi; Huang, Xiao Li; Gan, Hua

doi:10.1007/s00384-013-1678-9

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…PTEN promotes apoptosis (17), which contributes to the aggregation of UC (18). The present study observed the upregulation of PTEN in UC, and that it had an enhancing effect on the apoptosis of HCnEpCs induced by LPS.…”

Section: Discussionsupporting

confidence: 60%

Overexpression of circAtp9b in ulcerative colitis is induced by lipopolysaccharides and upregulates PTEN to promote the apoptosis of colonic epithelial cells

Фан

et al. 2021

Exp Ther Med

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It has been reported that knockdown of circular RNA (circ) ATPase class II type 9B (Atp9b) can reduce lipopolysaccharide (LPS)-induced inflammation, which plays a notable role in ulcerative colitis (UC). The present study aimed to explore the role of circAtp9b in UC. The expression levels of Atp9b and PTEN in the plasma of patients with UC (n=60) and healthy controls (n=60) were determined via reverse transcription-quantitative PCR. Overexpression of circAtp9b and PTEN were achieved in human colonic epithelial cells (HCnEpCs) to explore the relationship between circAtp9b and PTEN. The role of circAtp9b and PTEN in regulating the apoptosis of HCnEpCs under LPS treatment was evaluated using flow cytometry. The present study revealed that circAtp9b was upregulated in UC and that it was positively correlated with PTEN. In HCnEpCs, LPS treatment resulted in upregulation of circAtp9b in a dose-dependent manner. Moreover, overexpression of circAtp9b mediated the upregulation of PTEN in HCnEpCs, while silencing of circAtp9b decreased the expression levels of PTEN. Apoptosis analysis demonstrated that overexpression of circAtp9b and PTEN promoted the apoptosis of HCnEpCs. In addition, silencing of circAtp9b suppressed apoptosis. Moreover, overexpression of PTEN reduced the effects of silencing of circAtp9b. In conclusion, overexpression of circAtp9b in UC was induced by LPS and it positively upregulated PTEN to promote the apoptosis of HCnEpCs induced by LPS.

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Section: Discussionsupporting

confidence: 60%

Overexpression of circAtp9b in ulcerative colitis is induced by lipopolysaccharides and upregulates PTEN to promote the apoptosis of colonic epithelial cells

Фан

et al. 2021

Exp Ther Med

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“…By contrast, the tumor suppressor phosphatase and tensin homology deleted on chromosome 10 (PTEN) inhibits the actions of PI3K 38 . Because Akt signaling is important in CAC 39 , we assessed Akt activation in Aim2 −/− mice. Similar expression of total Akt (Fig.…”

Section: Resultsmentioning

confidence: 99%

Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt

Wilson

Petrucelli

Chen

et al. 2015

Nat Med

251

300

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The inflammasome activates caspase-1 and the release of interleukin-1β (IL-1β) and IL-18, and several inflammasomes protect against intestinal inflammation and colitis-associated colon cancer (CAC) in animal models. The absent in melanoma 2 (AIM2) inflammasome is activated by double-stranded DNA, and AIM2 expression is reduced in several types of cancer, but the mechanism by which AIM2 restricts tumor growth remains unclear. We found that Aim2-deficient mice had greater tumor load than Asc-deficient mice in the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colorectal cancer. Tumor burden was also higher in Aim2−/−/ApcMin/+ than in APCMin/+ mice. The effects of AIM2 on CAC were independent of inflammasome activation and IL-1β and were primarily mediated by a non–bone marrow source of AIM2. In resting cells, AIM2 physically interacted with and limited activation of DNA-dependent protein kinase (DNA-PK), a PI3K-related family member that promotes Akt phosphorylation, whereas loss of AIM2 promoted DNA-PK–mediated Akt activation. AIM2 reduced Akt activation and tumor burden in colorectal cancer models, while an Akt inhibitor reduced tumor load in Aim2−/− mice. These findings suggest that Akt inhibitors could be used to treat AIM2-deficient human cancers.

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“…3). Previous studies have shown that transduction of the wild-type PTEN gene into cancer cells induces apoptosis (25,26). Here, we observed that PTEN-VP22 enhanced apoptosis relative to PTEN alone, whereas VP22 had no effect on apoptosis levels (Fig.…”

Section: Discussionmentioning

confidence: 49%

Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo

Xia

et al. 2016

Oncology Reports

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In the past decade, studies have revealed that the phosphatase and tensin homolog (PTEN) protein, a tumor suppressor, comprises a potential biological marker and therapeutic target for esophageal squamous cell carcinoma (ESCC). As such, the delivery of the PTEN gene represents a powerful strategy for ESCC therapy. The tegument protein VP22 of herpes simplex virus type 1 (HSV-1) has been reported to act as a transporter of heterologous proteins across the host cell membrane, thereby enhancing the biological functions of these proteins. In the present study, the intercellular delivery and antitumor activity of the fusion protein PTEN-VP22 were examined in the esophageal squamous cell carcinoma cell line Eca109 both in vitro and in vivo. VP22-mediated PTEN intercellular delivery was confirmed in the Eca109 cells by western blot analysis and by quantitation of immunofluorescence. VP22 alone did not exert antiproliferative effects or induce cell cycle arrest, induction of apoptosis, blockage of the Akt and focal adhesion kinase (FAK) pathways, tumor growth inhibition, or antiangiogenic effects in Eca109 cells. However, compared with PTEN alone, PTEN-VP22 exerted significantly higher antiproliferative effects and induced cell cycle arrest at G1 stage, apoptosis and antiangiogenic effects in Eca109 cells. Together, our findings demonstrate that VP22 alone does not exert antitumor activity directly; however, this protein mediates the intercellular delivery of PTEN and thereby increases its intracellular concentration to achieve a therapeutic steady state, leading to an overall increase in the antitumor activity of PTEN. This study provides further experimental data to confirm the potential of VP22-based intercellular delivery strategies for enhancing the efficacy of gene therapy for cancer treatment.

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Effect of adenovirus-mediated PTEN gene on ulcerative colitis-associated colorectal cancer

Abstract: PTEN plays an important role in the inflammation-dysplasia-carcinoma sequence and may be a new molecular target in preventing and treating ulcerative colitis-associated colorectal cancer.

Cited by 9 publications

References 36 publications

Overexpression of circAtp9b in ulcerative colitis is induced by lipopolysaccharides and upregulates PTEN to promote the apoptosis of colonic epithelial cells

Overexpression of circAtp9b in ulcerative colitis is induced by lipopolysaccharides and upregulates PTEN to promote the apoptosis of colonic epithelial cells

Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt

Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo

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