Song Jun, Fu Qingsheng, Liu Gang, Zhang Chengxiong, Wang Yingying, Tao Shaoneng, Liu Rui, Li Zhi
Department of Laboratory Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province 241001, China.
Cancer Treat Res Commun. 2022;31:100551. doi: 10.1016/j.ctarc.2022.100551. Epub 2022 Mar 23.
Tubby-like protein 3 (TULP3) is a member of the tubby family, has been related to the development of nervous system by gene knockout researches. Nevertheless, the role of TULP3 in the gastric cancer is not clear.
Western blotting and real-time polymerase chain reaction (PCR) were employed for the quantitative detection of TULP3 expression in the gastric cancer and consecutive non-cancerous tissues, and gastric cancer cells. The roles of TULP3 in invasion, migration as well as proliferation of the gastric cancer cell in vivo and in vitro through utilizing colony formation, MTT, wound-healing, transwell and mouse xenograft model. Western blotting assay was implemented in order to clarify the potential molecular mechanisms. Furthermore, electron microscopy and western blot were evaluated TULP3 expression in gastric cancer patient extracted serum exosomes.
TULP3 expression levels were remarkably upregulated in the gastric cancer tissues and cells. Subsequent functional assays demonstrated that TULP3 downregulation suppressed invasion, migration as well as the proliferation of the gastric cancer cell. Mechanism assays depicted that the PTEN/Akt/Snail signaling pathway can inhibit invasion, migration as well as the proliferation of the gastric cancer cell via TULP3 silencing. Finally, we found that the expression of TULP3 could be determined in the extracted serum exosomes. The expression of TULP3 in gastric cancer group was higher in comparison with normal group.
Our results reveal that TULP3 might serve as a potential prognostic biomarker and therapeutic target for the treatment of gastric cancer.
类Tubby蛋白3（TULP3）是Tubby家族的成员，基因敲除研究表明其与神经系统发育有关。然而，TULP3在胃癌中的作用尚不清楚。
采用蛋白质免疫印迹法和实时聚合酶链反应（PCR）定量检测胃癌组织、癌旁组织及胃癌细胞中TULP3的表达。通过集落形成、MTT、伤口愈合、Transwell实验及小鼠异种移植模型，研究TULP3在体内外对胃癌细胞侵袭、迁移及增殖的作用。采用蛋白质免疫印迹法分析其潜在分子机制。此外，通过电子显微镜和蛋白质免疫印迹法评估胃癌患者血清外泌体中TULP3的表达。
TULP3在胃癌组织和细胞中的表达水平显著上调。随后的功能实验表明，下调TULP3可抑制胃癌细胞的侵袭、迁移及增殖。机制分析表明，PTEN/Akt/Snail信号通路可通过沉默TULP3抑制胃癌细胞的侵袭、迁移及增殖。最后，我们发现可在提取的血清外泌体中检测到TULP3的表达。胃癌组TULP3的表达高于正常组。
我们的研究结果表明，TULP3可能是胃癌潜在的预后生物标志物和治疗靶点。
