Inhibition of squalene epoxidase linking with PI3K/AKT signaling pathway suppresses endometrial cancer.
Inhibition of squalene epoxidase linking with PI3K/AKT signaling pathway suppresses endometrial cancer.
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子宫内膜癌(EC)是一种常见的恶性肿瘤，缺乏任何治疗靶点，在许多情况下，复发是女性发病率和死亡率的主要原因。众所周知，EC与脂代谢异常呈显著正相关。角鲨烯环氧酶(SQLE)是胆固醇合成途径中的关键酶，调节脂质代谢过程，近年来被发现与多种癌症有关。在这里，我们重点研究了SQLE在电子商务中的作用。我们的研究表明，Sqle在EC组织中的表达水平显著上调。体外实验表明，Sqle过表达明显促进EC细胞增殖，抑制细胞凋亡，而Sqle基因敲除或应用特比奈芬则相反。此外，我们还发现SQLE对EC细胞增殖的促进作用可能是通过激活PI3K/AKT通路实现的。在体内，研究证实，SQLE或特比奈芬的击倒可以显著地抑制裸鼠体内的肿瘤生长。这些结果表明，SQLE可能通过激活PI3K/AKT通路促进EC的进展。此外，SQLE是治疗EC的潜在靶点，其抑制剂特比奈芬有可能成为治疗EC的靶向药物。我们发现Sqle在EC组织中的表达水平显著上调。体外实验表明，Sqle过表达可显著促进EC细胞的增殖和迁移。耐人寻味的是，Sqle的抑制剂特比奈芬可以显著抑制EC细胞的活性。此外，我们还发现SQLE对EC细胞增殖和迁移的促进作用可能是通过激活PI3K/AKT途径实现的。体内研究表明，SQLE基因敲除后能显著抑制裸鼠体内肿瘤生长。
Endometrial cancer (EC) is a common malignant tumor that lacks any therapeutic target and, in many cases, recurrence is the leading ca use of morbidity and mortality in women. Widely known EC has a strongly positive correlation with abnormal lipid metabolism. Squalene epoxidase (SQLE), a crucial enzyme in the cholesterol synthesis pathway regulating lipid metabolic processes has been found to be associated with various cancers in recent years. Here, we focused on studying the role of SQLE in EC. Our study revealed that SQLE expression level was upregulated significantly in EC tissues. In vitro experiments showed that SQLE overexpression significantly promoted the proliferation, and inhibited cell apoptosis of EC cells, whereas SQLE knockdown or use of terbinafine showed the opposite results. Furthermore, we found out that the promotional effect of SQLE on the proliferation of EC cells might be achieved by activating the PI3K/AKT pathway. In vivo, studies confirmed that the knockdown of SQLE or terbinafine can observably inhibit tumor growth in nude mice. These results indicate that SQLE may promote the progression of EC by activating the PI3K/AKT pathway. Moreover, SQLE is a potential target for EC treatment and its inhibitor, terbinafine, has the potential to become a targeted drug for EC treatment. We identified that SQLE expression level was upregulated significantly in EC tissues. In vitro experiments showed that SQLE overexpression significantly promoted the proliferation and migration of EC cells. Intriguing, terbinafine, an inhibitor of SQLE, could significantly inhibit EC cell activity. Furthermore, we found that the enhancing effect of SQLE on the proliferation and migration of EC cells might be achieved by activating the PI3K/AKT pathway. In vivo studies showed that the knockdown of SQLE could noticeably inhibit tumor growth in nude mice.
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影响因子：
9.2
作者：
Li, Jing;Yang, Tao;Wang, Qihong;Li, Yuedan;Wu, Haiyan;Zhang, Mei;Qi, Hong;Zhang, Hongxin;Li, Jinfeng
通讯作者：
Li, Jinfeng
DOI：
10.1073/pnas.2018578117
发表时间：
2020-11-10
影响因子：
11.1
作者：
Kober, Daniel L.;Xu, Shimeng;Radhakrishnan, Arun
通讯作者：
Radhakrishnan, Arun
影响因子：
8.8
作者：
Kuzu, Omer F.;Gowda, Raghavendra;Robertson, Gavin P.
通讯作者：
Robertson, Gavin P.
影响因子：
29
作者：
Goossens, Pieter;Rodriguez-Vita, Juan;Lawrence, Toby
通讯作者：
Lawrence, Toby
影响因子：
29.4
作者：
Liu, Dabin;Wong, Chi Chun;Yu, Jun
通讯作者：
Yu, Jun