Feng Yifei, Ji Dongjian, Huang Yuanjian, Ji Bing, Zhang Yue, Li Jie, Peng Wen, Zhang Chuan, Zhang Dongsheng, Sun Yueming, Xu Ziwei
Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Department of General Surgery, Yancheng City No. 1 People's Hospital, Yancheng, Jiangsu 224005, P.R. China.
Oncol Rep. 2020 Mar;43(3):864-876. doi: 10.3892/or.2020.7474. Epub 2020 Jan 21.
The dysregulation of transcription factors contributes to the unlimited proliferation of cancer cells. Transglutaminase 3 (TGM3) has been demonstrated to play a crucial role in physiology and pathology. However, the potential role of TGM3 in colorectal cancer (CRC) remains unknown. In the present study, reverse transcription‑quantitative PCR and immunohistochemistry were utilized to analyze the expression of TGM3 in CRC and adjacent normal tissues. LoVo and HCT116 cell lines were then selected to further investigate the function of TGM3 in the proliferation, invasion and metastasis of CRC both in vitro and in vivo. Finally, western blotting was performed to investigate the molecular mechanisms underlying the effects of TGM3 in CRC. The expression level of TGM3 was significantly downregulated in CRC tissues, and was associated with tumor invasion, metastasis and patient prognosis. Following TGM3 inhibition and overexpression in CRC cells, it was revealed that TGM3 suppressed cell proliferation, potentially via the promotion of apoptosis and cell cycle regulation. Furthermore, TGM3 also inhibited invasion and metastasis. Finally, it was observed that TGM3 inhibited epithelial‑to‑mesenchymal transition and activated phosphorylated AKT serine/threonine kinase in CRC cells. The results from the present study revealed that TGM3 is a tumor suppressor in the progression of CRC, and may be used as a novel target for CRC treatment.
转录因子的失调促成了癌细胞的无限增殖。转谷氨酰胺酶3（TGM3）已被证明在生理和病理过程中起关键作用。然而，TGM3在结直肠癌（CRC）中的潜在作用仍不清楚。在本研究中，利用逆转录定量PCR和免疫组织化学分析TGM3在CRC组织和癌旁正常组织中的表达。然后选择LoVo和HCT116细胞系，进一步研究TGM3在体外和体内对CRC增殖、侵袭和转移的作用。最后，进行蛋白质印迹法以研究TGM3在CRC中发挥作用的分子机制。TGM3在CRC组织中的表达水平显著下调，且与肿瘤侵袭、转移及患者预后相关。在CRC细胞中抑制和过表达TGM3后发现，TGM3可能通过促进细胞凋亡和调控细胞周期来抑制细胞增殖。此外，TGM3还抑制侵袭和转移。最后观察到，TGM3抑制CRC细胞的上皮-间质转化并激活磷酸化的AKT丝氨酸/苏氨酸激酶。本研究结果表明，TGM3在CRC进展中是一种肿瘤抑制因子，可能作为CRC治疗的新靶点。
