KIF22 promotes the proliferation and immune escape of endometrial cancer cells by activating the STAT3/PDL1 pathway.

IF 2 4区 生物学 Q3 CELL BIOLOGY
Chaoqun Wang, Chaohe Zhang
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引用次数: 0

Abstract

Objective: Endometrial cancer (EC) is a common gynecologic malignancy with high morbidity and mortality. Kinesin Family member 22 (KIF22) is regarded as a critical oncogene, but its functions in EC progression remained elusive. Hence, this research elucidated the role of KIF22 in EC development and studied the possible mechanism.

Methods: KIF22 expression in EC and the relationship with the overall survival of EC cases were determined by GEPIA and online K-M plotter. After transfection with sh-KIF22, cell viability and invasion were evaluated utilizing CCK-8 and Transwell assays. The content of IFN-γ, IL-2, and TNF-α was assessed utilizing an ELISA assay. The protein levels of p-STAT3, STAT3, and PD-L1 were examined using western blot. A xenograft tumor was constructed to assess tumor growth.

Results: KIF22 was elevated in EC, with high KIF22 levels presenting poor overall survival. Additionally, silenced KIF22 restrained EC cell viability, invasion ability, and STAT3/PD-L1 pathway, enhanced the viability of CD8+ T cells, and elevated the levels of IFN-γ, IL-2, and TNF-α. Moreover, the rescue assay revealed that STAT3 overexpression counteracted the inhibitory effect of silenced KIF22 on EC cell proliferation, invasion and immune escape. Furthermore, silenced KIF22 repressed EC tumor growth and p-STAT3 and PD-L1 levels, and elevated the IFN-γ level in vivo.

Conclusion: The findings demonstrated that KIF22 was elevated in EC and correlated with a poor prognosis. Silenced KIF22 repressed cell proliferation, invasion, and immune escape via suppressing the STAT3/PD-L1 pathway in EC.

KIF22通过激活STAT3/PDL1通路促进子宫内膜癌细胞的增殖和免疫逃逸。
目的:子宫内膜癌是一种常见的妇科恶性肿瘤,发病率高,死亡率高。Kinesin家族成员22 (KIF22)被认为是一个关键的癌基因,但其在EC进展中的功能尚不清楚。因此,本研究阐明了KIF22在EC发育中的作用,并研究了其可能的机制。方法:采用GEPIA和在线K-M绘图仪检测KIF22在EC中的表达及其与EC患者总生存率的关系。转染sh-KIF22后,采用CCK-8和Transwell检测细胞活力和侵袭性。采用ELISA法测定IFN-γ、IL-2和TNF-α的含量。western blot检测p-STAT3、STAT3、PD-L1蛋白水平。构建异种移植物肿瘤以评估肿瘤生长情况。结果:KIF22在EC中升高,高水平的KIF22表现为较差的总生存率。此外,沉默的KIF22抑制EC细胞的活力、侵袭能力和STAT3/PD-L1通路,增强CD8+ T细胞的活力,提高IFN-γ、IL-2和TNF-α的水平。此外,拯救实验显示STAT3过表达抵消了沉默的KIF22对EC细胞增殖、侵袭和免疫逃逸的抑制作用。此外,沉默的KIF22抑制EC肿瘤生长和p-STAT3和PD-L1水平,并在体内升高IFN-γ水平。结论:KIF22在EC中升高,与预后不良相关。沉默的KIF22通过抑制EC中STAT3/PD-L1通路抑制细胞增殖、侵袭和免疫逃逸。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Histology and histopathology
Histology and histopathology 生物-病理学
CiteScore
3.90
自引率
0.00%
发文量
232
审稿时长
2 months
期刊介绍: HISTOLOGY AND HISTOPATHOLOGY is a peer-reviewed international journal, the purpose of which is to publish original and review articles in all fields of the microscopical morphology, cell biology and tissue engineering; high quality is the overall consideration. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year (more than 1,300 pages, approximately 90 original works and 40 reviews). Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online.
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