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SEC61G 通过激活 MAPK 信号通路促进宫颈癌增殖。

SEC61G Promotes Cervical Cancer Proliferation by Activating MAPK Signaling Pathway.

机构信息

Department of Obstetrics and Gynecology, Shaanxi Province People's Hospital, Xi'an, 710068 Shaanxi, China.

出版信息

Dis Markers. 2022 Aug 31;2022:7016079. doi: 10.1155/2022/7016079. eCollection 2022.

DOI:10.1155/2022/7016079
PMID:36092956
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9452971/
Abstract

OBJECTIVE

The abnormal expression of SEC61G plays an important role in the development of various tumors. This study explored the effects of SEC61G on MAPK signaling pathway and proliferation of cervical cancer (CC) cells.

METHODS

shRNA was used to inhibit the expression of SEC61G and EdU to observe its effect on the proliferation of CC cell SiHa. The effect of SEC61G on invasion was evaluated by Transwell assay. TCGA database was used to analyze the influence of high or low SEC61G expression level on the overall survival of CC patients. Western blot was used to detect the expressions of SEC61G, p-RAF1, Raf1, p-MEK1/2, MEK1/2, and p-ERK1/2 in cells. SiHa cells overexpressing SEC61G (SiHa-SEC61G) and control group (SiHa-mock) were subcutaneously implanted in nude mice. The tumor growth curve was measured at the specified time points between SiHa-SEC61G and SiHa-mock. The inhibitory effect of gefitinib on SEC61G was further evaluated.

RESULTS

In patients with CC, high SEC61G expression predicted poor prognosis. Silencing SEC61G inhibited proliferation and invasion of CC cells in vitro. Overexpression of SEC61G can promote the proliferation and invasion of CC cells in vitro. Meanwhile, overexpression of SEC61G promoted the proliferation of CC xenografts. Knocking down SEC61G can inhibit MAPK signaling pathway. Gefitinib can inhibit CC proliferation and tumor growth by SEC61G.

CONCLUSION

SEC61G is highly expressed in CC and has poor prognosis. Inhibition of SEC61G expression can effectively inhibit the growth and proliferation of human CC cells. The mechanism may be related to the inhibition of MAPK signaling pathway.

摘要

目的

SEC61G 的异常表达在各种肿瘤的发生发展中起着重要作用。本研究探讨了 SEC61G 对 MAPK 信号通路和宫颈癌(CC)细胞增殖的影响。

方法

利用 shRNA 抑制 SEC61G 的表达,并用 EdU 观察其对 CC 细胞 SiHa 增殖的影响。通过 Transwell 实验评估 SEC61G 对侵袭的影响。TCGA 数据库用于分析 SEC61G 高或低表达水平对 CC 患者总生存期的影响。Western blot 用于检测细胞中 SEC61G、p-RAF1、Raf1、p-MEK1/2、MEK1/2 和 p-ERK1/2 的表达。将过表达 SEC61G 的 SiHa 细胞(SiHa-SEC61G)和对照组(SiHa-mock)皮下注射到裸鼠中。在指定时间点测量 SiHa-SEC61G 和 SiHa-mock 之间的肿瘤生长曲线。进一步评估吉非替尼对 SEC61G 的抑制作用。

结果

在 CC 患者中,SEC61G 高表达预示着预后不良。沉默 SEC61G 抑制 CC 细胞的体外增殖和侵袭。SEC61G 的过表达可以促进 CC 细胞的体外增殖和侵袭。同时,SEC61G 的过表达促进了 CC 异种移植的增殖。敲低 SEC61G 可以抑制 MAPK 信号通路。吉非替尼可以通过 SEC61G 抑制 CC 的增殖和肿瘤生长。

结论

SEC61G 在 CC 中高表达,且预后不良。抑制 SEC61G 的表达可以有效抑制人 CC 细胞的生长和增殖。其机制可能与抑制 MAPK 信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/0412551ca5f9/DM2022-7016079.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/4b9635af8c4a/DM2022-7016079.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/f3c3c39ba7db/DM2022-7016079.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/dc2c0daf27a6/DM2022-7016079.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/eb4cd2666606/DM2022-7016079.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/f71275955e7d/DM2022-7016079.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/0412551ca5f9/DM2022-7016079.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/4b9635af8c4a/DM2022-7016079.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/f3c3c39ba7db/DM2022-7016079.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/dc2c0daf27a6/DM2022-7016079.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/eb4cd2666606/DM2022-7016079.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/f71275955e7d/DM2022-7016079.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bdf/9452971/0412551ca5f9/DM2022-7016079.006.jpg

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