Bao Xian-Yi, Sun Ming, Peng Ting-Ting, Han Dong-Mei
Department of Cataract, Aier Eye Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Fundus Disease, Huainan Chenguang Eye Hospital, Huainan, Anhui, China.
Cancer Biomark. 2021;31(4):307-315. doi: 10.3233/CBM-200050.
Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which has been determined in various cancers, including renal cell carcinoma, acute promyelocytic leukemia, colorectal cancer, endometrial cancer, and glioma. However, its role in retinoblastoma (RB) has not yet been explored.
The expression level of TRIB3 was detected in RB tissues and cell lines using qRT-PCR. The effects of TRIB3 on cell proliferation and invasion capacities were analyzed with MTT, crystal violet, and transwell assays. Western blot and rescue assays were conducted to explore the underlying mechanism.
This study found that TRIB3 was upregulated in human RB tissues compared to adjacent normal tissues both at the mRNA and protein levels. Overexpression of TRIB3 significantly promoted cell proliferation and invasion of RB cells, while TRIB3 knockdown inhibited these processes. Moreover, the mechanism deciphering experiments showed that TRIB3 overexpression can increase AKT and mTOR phosphorylation. Conversely, TRIB3 knockdown decreased the phosphorylation of AKT and mTOR. Additionally, MK2206, a potent AKT inhibitor, blocked the promotive effects of TRIB3 in RB cells.
This study demonstrated that TRIB3 acts as an oncogene and plays a crucial role in the proliferation and invasion of RB cells via regulating the AKT/mTOR signaling pathway. Therefore, TRIB3 may serve as a potential target in the diagnosis and/or treatment of RB.
Tribbles假激酶3（TRIB3）是tribbles相关家族的成员，已在多种癌症中得到证实，包括肾细胞癌、急性早幼粒细胞白血病、结直肠癌、子宫内膜癌和神经胶质瘤。然而，其在视网膜母细胞瘤（RB）中的作用尚未得到探索。
使用qRT-PCR检测RB组织和细胞系中TRIB3的表达水平。通过MTT、结晶紫和Transwell实验分析TRIB3对细胞增殖和侵袭能力的影响。进行蛋白质免疫印迹和挽救实验以探索潜在机制。
本研究发现，与相邻正常组织相比，人RB组织中TRIB3在mRNA和蛋白质水平均上调。TRIB3的过表达显著促进RB细胞的增殖和侵袭，而TRIB3的敲低则抑制这些过程。此外，机制解析实验表明，TRIB3的过表达可增加AKT和mTOR的磷酸化。相反，TRIB3的敲低降低了AKT和mTOR的磷酸化。此外，强效AKT抑制剂MK2206可阻断TRIB3对RB细胞的促进作用。
本研究表明，TRIB3作为一种癌基因，通过调节AKT/mTOR信号通路在RB细胞的增殖和侵袭中起关键作用。因此，TRIB3可能作为RB诊断和/或治疗的潜在靶点。
