Anti‐oncogenic PTEN induces ovarian cancer cell senescence by targeting P21

Abstract

Deletion and mutation of phosphatase and tensin homolog deleted on chromosome10 (PTEN) are closely associated with the occurrence of tumors. Tumor suppressor gene PTEN mutation plays an important role in the pathogenesis of ovarian cancer. However, it has been unclear whether it can regulate the senescence of ovarian cancer cells. We speculated that PTEN might inhibit the occurrence and development of ovarian cancer by promoting the expression of P21. We found that the expression of TRIM39 in human ovarian cancer was significantly diminished. In SKOV3 cells treated with naringin, the expression of TRIM39, which binds P21 and inhibits P21 degradation, was significantly elevated. Real‐time polymerase chain reaction (PCR), Western blot, and immunofluorescence were used to detected the expression of PTEN, p21, and TRIM39, β‐galactosidase Staining was used to detect cell senescence, Ki67 staining was used to observe cell proliferation, Trim39 interference or overexpression assay was used to detect its function. We speculated that PTEN might promote SKOV3 cell senescence by increasing TRIM39 expression and decreasing P21 degradation. Furthermore, by interfering with TRIM39 in SKOV3 cells, we found that the expression of P21 was downregulated, and the number of senescent SKOV3 cells decreased. With overexpression of TRIM39 in SKOV3 cells, the expression of P21 was upregulated, and the number of senescent SKOV3 cells increased. When naringin, a PTEN agonist, was added to SKOV3 cells in which TRIM39 protein was interfered with, the expression of P21 was significantly lower than that in the control group, and the number of senescent ovarian cancer cells was significantly diminished. Our results indicated that PTEN maintained the stability of P21 and decreased the degradation of P21 by increasing TRIM39 expression, thus promoting the senescence of SKOV3 cells, and PTEN maintained the stability of p21 and promoted the aging of SKOV3 cells might be a novel therapeutic target for ovarian cancer.

Complexity of the Genetic Background of Oncogenesis in Ovarian Cancer—Genetic Instability and Clinical Implications

“…Somatic PTEN mutations, combined with KRAS mutations, may predispose to invasive and metastatic endometrioid ovarian cancer. Targeted therapies for these mutations in ovarian cancer type I have been unsatisfactory [82,83]. Ovarian cancer risk-reducing surgery is not recommended for PTEN pathogenic variant carriers, but they face an increased risk of endometrial cancer (approximately 5-10%) [76].…”

Mechanisms of Senescence in Cancer: Positive and Negative Aspects of Cancer Cells Senescence

“…In the ovarian cell line, overexpression of PTEN promoted ageing by promoting p21 expression. Ke et al (2021) showed that PTEN increased TRIM39 expression, which binds to p21 and inhibits p21 degradation [65]. In human lung adenocarcinoma A549 cells, siPTEN accelerated bleomycin-induced premature senescence by increasing the expression of the p16, p21 protein and increasing SA-β-gal activity.…”

“…Cell senescence could affect the promotion of cell-autonomous reprogramming of non-stem cancer cells into cancer stem cells [129,125]. The important mediators of senescenceinduced cell reprogramming are the transcription factors Oct4, Sox2, Klf4, c-Myc (OSKM), and IL-6, while expression could depend on the absence of loci INK4a and p53 [65,[129][130][131].…”

Naringin inhibits cisplatin resistance of ovarian cancer cells by inhibiting autophagy mediated by the TGF-β2/smad2 pathway

“…It is involved in and regulates various activities and signal transduction processes in cancer development ( 8 ). Naringin is commonly used as a phosphatase and tensin homolog agonist to interfere with the biological action of OC cells ( 9 ). In animal experiments, naringin inhibits tumor growth ( 10 ).…”