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TIMELESS通过增强卵巢癌中巨噬细胞的募集促进肿瘤进展。

TIMELESS Promotes Tumor Progression by Enhancing Macrophages Recruitment in Ovarian Cancer.

作者信息

Xing Xin, Gu Fei, Hua Lanyu, Cui Xiaoxiao, Li Dongxue, Wu Zhiyong, Zhang Rong

机构信息

Department of Obstetrics and Gynecology, Fengxian Hospital Affiliated to the Southern Medical University, Shanghai, China.

The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.

出版信息

Front Oncol. 2021 Aug 19;11:732058. doi: 10.3389/fonc.2021.732058. eCollection 2021.

DOI:10.3389/fonc.2021.732058
PMID:34490127
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8417241/
Abstract

OBJECTIVE

Ovarian cancer (OV) is the most fatal and frequent type of gynecological malignancy worldwide. TIMELESS (TIM), as a circadian clock gene, has been found to be highly expressed and predictive of poor prognosis in various cancers. However, the function of TIM in OV is not known. This study was designed to investigate the biological functions and underlying mechanisms of TIM during OV progression.

METHODS

Cell viability assay, cell migration assay, immunohistochemistry staining, qPCR analyses, and tumor xenograft model were used to identify the functions of TIM in OV. Bioinformatics analyses, including GEPIA, cBioPortal, GeneMANIA, and TIMER, were used to analyze the gene expression, genetic alteration, and immune cell infiltration of TIM in OV.

RESULTS

TIM is highly expressed in OV patients. TIM knockdown inhibited OV cell proliferation, migration, and invasion both and . Genetic alteration of TIM was identified in patients with OV. TIM co-expression network indicates that TIM had a wide effect on the immune cell infiltration and activation in OV. Further analysis and experimental verification revealed that TIM was positively correlated with macrophages infiltration in OV.

CONCLUSIONS

Our study unveiled a novel function of highly expressed TIM associated with immune cell especially macrophages infiltration in OV. TIM may serve as a potential prognostic biomarker and immunotherapy target for OV patients.

摘要

目的

卵巢癌（OV）是全球最致命且最常见的妇科恶性肿瘤类型。作为一种昼夜节律时钟基因，永恒蛋白（TIM）已被发现在多种癌症中高表达且预示着不良预后。然而，TIM在OV中的功能尚不清楚。本研究旨在探讨TIM在OV进展过程中的生物学功能及潜在机制。

方法

采用细胞活力测定、细胞迁移测定、免疫组织化学染色、qPCR分析和肿瘤异种移植模型来确定TIM在OV中的功能。利用包括GEPIA、cBioPortal、GeneMANIA和TIMER在内的生物信息学分析来分析TIM在OV中的基因表达、基因改变和免疫细胞浸润情况。

结果

TIM在OV患者中高表达。敲低TIM可抑制体外和体内OV细胞的增殖、迁移和侵袭。在OV患者中发现了TIM的基因改变。TIM共表达网络表明TIM对OV中的免疫细胞浸润和激活有广泛影响。进一步分析和实验验证显示，TIM与OV中的巨噬细胞浸润呈正相关。

结论

我们的研究揭示了高表达的TIM与OV中免疫细胞尤其是巨噬细胞浸润相关的新功能。TIM可能作为OV患者潜在的预后生物标志物和免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/8039315f7e5b/fonc-11-732058-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/ec82b35183ae/fonc-11-732058-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/43a483a1ab12/fonc-11-732058-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/c482438a724e/fonc-11-732058-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/5ee3fb2a3746/fonc-11-732058-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/8039315f7e5b/fonc-11-732058-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/ec82b35183ae/fonc-11-732058-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/43a483a1ab12/fonc-11-732058-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/c482438a724e/fonc-11-732058-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/5ee3fb2a3746/fonc-11-732058-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2605/8417241/8039315f7e5b/fonc-11-732058-g005.jpg

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Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9.组蛋白 H3k27 乙酰化激活时钟基因 TIMELESS 通过与肌球蛋白-9 结合促进结直肠癌肿瘤发生。
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Night shift schedule causes circadian dysregulation of DNA repair genes and elevated DNA damage in humans.
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An integrative evaluation of circadian gene TIMELESS as a pan-cancer immunological and predictive biomarker.生物钟基因 TIMELESS 作为一种泛癌免疫和预测性生物标志物的综合评估。
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TIMELESS upregulates PD-L1 expression and exerts an immunosuppressive role in breast cancer.无时间性上调 PD-L1 的表达，并在乳腺癌中发挥免疫抑制作用。
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