TRIB1通过诱导上皮-间质转化进程促进卵巢癌细胞的增殖和迁移。

TRIB1 facilitates the proliferation and migration of ovarian cancer cells by inducing EMT progression.

作者信息

Shi Guangyan, Holgersson Kristian, Xin Zhen, Szekely Laszlo, Du Qiqiao, Jing Xu

机构信息

Medical Laboratory center, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China.

Loma Linda University, CA, USA.

出版信息

Histol Histopathol. 2025 Sep;40(9):1447-1455. doi: 10.14670/HH-18-868. Epub 2024 Dec 31.

DOI:10.14670/HH-18-868

PMID:39807763

Abstract

AIM

Ovarian cancer (OC) is a fatal female malignant tumor that severely impacts the health of women worldwide. Due to the lack of diagnostic biomarkers, 70% of OC patients are considered in the advanced stage at the first diagnosis. Exploring novel biomarkers for OC diagnosis has become an urgent clinical need to address. TRIB1 is a newly discovered oncogene in several malignant tumors, including acute myeloid leukemia, prostate cancer, and breast cancer. However, the biological function of TRIB1 in OC remains uncertain and, therefore, was explored in the present study.

METHODS

Levels of TRIB1 in OC and normal tissues were evaluated in the GEPIA database. TRIB1-KD was constructed in ES-2 cells and TRIB1-OE was constructed in OVCAR3 cells using a siRNA and OE vector, respectively. The proliferation ability was determined using the CCK-8 and clone formation assays. The migration ability was detected using the wound healing and Transwell assays. The expression of epithelial-mesenchymal transition (EMT) biomarkers was determined using western blotting.

RESULTS

TRIB1 was markedly upregulated in OC tissues compared with normal ovarian tissues in the GEPIA database. The TRIB1 level was slightly altered among ES-2, CAOV3, and SKOV3 cells, with the highest expression in ES-2 cells, which was greatly reduced in OVCAR3 cells. In TRIB1-KD ES-2 cells, a remarkably reduced proliferation ability was observed with the CCK-8 and clone formation assays, accompanied by a reduction in migration distance in the Wound healing assay and the number of migrated cells in the Transwell assay. In contrast, in TRIB1-OE OVCAR3 cells, increased proliferation ability was observed, accompanied by increased migration distance and number of migrated cells. Furthermore, EMT progression was markedly repressed in TRIB1-KD ES-2 cells and remarkably enhanced in TRIB1-OE OVCAR3 cells.

CONCLUSION

TRIB1 facilitated the proliferation and migration of OC cells by enhancing EMT progression.

摘要

目的

卵巢癌（OC）是一种致命的女性恶性肿瘤，严重影响全球女性的健康。由于缺乏诊断生物标志物，70%的OC患者在首次诊断时被认为处于晚期。探索用于OC诊断的新型生物标志物已成为亟待解决的临床需求。TRIB1是在几种恶性肿瘤（包括急性髓系白血病、前列腺癌和乳腺癌）中新发现的一种癌基因。然而，TRIB1在OC中的生物学功能仍不确定，因此在本研究中对其进行了探索。

方法

在GEPIA数据库中评估OC组织和正常组织中TRIB1的水平。分别使用小干扰RNA和过表达载体在ES-2细胞中构建TRIB1基因敲低（TRIB1-KD）和在OVCAR3细胞中构建TRIB1过表达（TRIB1-OE）。使用CCK-8和克隆形成试验测定增殖能力。使用伤口愈合试验和Transwell试验检测迁移能力。使用蛋白质免疫印迹法测定上皮-间质转化（EMT）生物标志物的表达。

结果

与GEPIA数据库中的正常卵巢组织相比，TRIB1在OC组织中明显上调。TRIB1水平在ES-2、CAOV3和SKOV3细胞中略有变化，在ES-2细胞中表达最高，在OVCAR3细胞中大幅降低。在TRIB1-KD的ES-2细胞中，CCK-8和克隆形成试验观察到增殖能力显著降低，同时伤口愈合试验中的迁移距离和Transwell试验中的迁移细胞数量减少。相反，在TRIB1-OE的OVCAR3细胞中，观察到增殖能力增加，同时迁移距离和迁移细胞数量增加。此外，在TRIB1-KD的ES-2细胞中EMT进程明显受到抑制，而在TRIB1-OE的OVCAR3细胞中显著增强。