Zhang Minmin, Li Feifei, Wang Jing, He Wenzhu, Li Yun, Li Hongyan, Wei Zhaolian, Cao Yunxia
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People's Republic of China.
Anhui Province Key Laboratory of Reproductive Health and Genetics, Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, People's Republic of China.
Onco Targets Ther. 2019 Aug 16;12:6371-6383. doi: 10.2147/OTT.S206861. eCollection 2019.
High-grade serous ovarian cancer (HGSOC) is one of the most common ovarian epithelial malignancies. tRNA-derived fragments (tRFs) have been identified as novel potential biomarkers and targets for cancer therapy. Nevertheless, the influence of tRFs on HGSOC remains unknown. This study aimed to identify HGSOC-associated tRFs and to investigate the function and mechanism of key tRFs in SK-OV-3 ovarian cancer cells.
The tRF profiles in HGSOC patients and controls were investigated using small RNA sequencing. Differentially expressed tRFs were verified by real-time PCR, and a key tRF was evaluated in a function study.
A total of 27 tRFs were differentially expressed between HGSOC patients and controls. Differentially expressed tRFs were mainly involved in the functions of protein phosphorylation, transcription and cell migration and the pathway of cancer, and the MAPK and Wnt signaling pathways. Real-time PCR verified that tRF-03357 and tRF-03358 were significantly increased in the HGSOC serum samples and SK-OV-3 cells compared to their expression levels in the controls. Importantly, tRF-03357 promoted SK-OV-3 cell proliferation, migration and invasion. Moreover, tRF-03357 was predictively targeted, and significantly downregulated HMBOX1.
This study suggests that tRF-03357 might promote cell proliferation, migration and invasion, partly by modulating HMBOX1 in HGSOC.
高级别浆液性卵巢癌(HGSOC)是最常见的卵巢上皮性恶性肿瘤之一。tRNA衍生片段(tRFs)已被确定为癌症治疗的新型潜在生物标志物和靶点。然而,tRFs对HGSOC的影响仍不清楚。本研究旨在鉴定与HGSOC相关的tRFs,并研究关键tRFs在SK-OV-3卵巢癌细胞中的功能和机制。
采用小RNA测序技术研究HGSOC患者和对照组的tRF谱。通过实时PCR验证差异表达的tRFs,并在功能研究中评估关键tRF。
HGSOC患者和对照组之间共有27个tRFs差异表达。差异表达的tRFs主要参与蛋白质磷酸化、转录和细胞迁移功能以及癌症通路、MAPK和Wnt信号通路。实时PCR验证,与对照组相比,tRF-03357和tRF-03358在HGSOC血清样本和SK-OV-3细胞中的表达显著增加。重要的是,tRF-03357促进SK-OV-3细胞增殖、迁移和侵袭。此外,tRF-03357被预测为靶点,并显著下调HMBOX1。
本研究表明,tRF-03357可能通过调节HGSOC中的HMBOX1促进细胞增殖、迁移和侵袭。