Department of Obstetrics and Gynecology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
Cell Biol Int. 2022 Jan;46(1):118-128. doi: 10.1002/cbin.11709. Epub 2021 Oct 19.
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.
PTEN 缺失和突变与肿瘤的发生密切相关。抑癌基因 PTEN 突变在卵巢癌的发病机制中起重要作用。然而，PTEN 是否能调节卵巢癌细胞的衰老尚不清楚。我们推测，PTEN 可能通过促进 P21 的表达来抑制卵巢癌的发生和发展。我们发现，人卵巢癌细胞中 TRIM39 的表达明显减少。在柚皮苷处理的 SKOV3 细胞中，与 P21 结合并抑制 P21 降解的 TRIM39 表达明显升高。实时聚合酶链反应（PCR）、Western blot 和免疫荧光检测 PTEN、p21 和 TRIM39 的表达，β-半乳糖苷酶染色检测细胞衰老，Ki67 染色观察细胞增殖，TRIM39 干扰或过表达实验检测其功能。我们推测，PTEN 可能通过增加 TRIM39 表达和减少 P21 降解来促进 SKOV3 细胞衰老。此外，通过干扰 SKOV3 细胞中的 TRIM39，我们发现 P21 的表达下调，衰老 SKOV3 细胞的数量减少。在 SKOV3 细胞中过表达 TRIM39 后，P21 的表达上调，衰老 SKOV3 细胞的数量增加。当在 TRIM39 蛋白被干扰的 SKOV3 细胞中加入柚皮苷（PTEN 激动剂）时，P21 的表达明显低于对照组，衰老的卵巢癌细胞数量明显减少。我们的结果表明，PTEN 通过增加 TRIM39 表达来维持 P21 的稳定性，减少 P21 的降解，从而促进 SKOV3 细胞衰老，PTEN 通过增加 TRIM39 表达维持 P21 的稳定性并促进 SKOV3 细胞衰老可能成为卵巢癌的一个新的治疗靶点。
