Liu Rui-Ting, Wang Guo-Rong, Liu Chang, Qiu Jian, Yan Li-Kun, Li Xiao-Jun, Wang Xiao-Qiang
Department of Hepatobiliary Surgery, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of General Surgery, The Third Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
Int J Mol Med. 2016 Sep;38(3):703-12. doi: 10.3892/ijmm.2016.2662. Epub 2016 Jul 4.
DNA binding protein A (dbpA) belongs to the Y-box binding protein family and has been reported to play an important role in carcinogenesis. Our previous study demonstrated that the knockdown of dbpA in gastric cancer cells inhibited cell proliferation by modulating the cell cycle. However, the role of dbpA in human colorectal cancer (CRC) remains unclear. In this study, immunohistochemical (IHC) staining and clinicopathological parameter analysis were employed to detect dbpA expression in 44 paired CRC samples and 7 CRC cell lines. Lentivirus-mediated short hairpin RNA (shRNA) was used to silence dbpA, and the effects of dbpA knockdown on cell proliferation were determined by MTT assay, colony formation assay and flow cytometry. Furthermore, a xenograft model was established to observe tumor growth in vivo. Functional analysis indicated that dbpA was overexpressed in the CRC tissues and cell lines, and a high dbpA expression was associated with the depth of invasion (p<0.001), the degree of differentiation (p<0.001), lymphatic metastasis (p<0.001) and vessel invasion (p<0.001). The suppression of dbpA expression resulted in decreased cell proliferation in vitro and tumor growth in vivo, and it induced cell cycle arrest and promoted the apoptosis of the CRC cells. As a whole, our findings illustrate the crucial role of dbpA in colorectal tumorigenesis. Thus, dbpA may be used as a novel and potent therapeutic target in CRC.
DNA结合蛋白A（dbpA）属于Y盒结合蛋白家族，据报道在致癌过程中发挥重要作用。我们之前的研究表明，敲低胃癌细胞中的dbpA可通过调节细胞周期来抑制细胞增殖。然而，dbpA在人类结直肠癌（CRC）中的作用仍不清楚。在本研究中，采用免疫组织化学（IHC）染色和临床病理参数分析来检测44对CRC样本和7种CRC细胞系中dbpA的表达。利用慢病毒介导的短发夹RNA（shRNA）使dbpA沉默，并通过MTT法、集落形成试验和流式细胞术确定敲低dbpA对细胞增殖的影响。此外，建立了异种移植模型以观察体内肿瘤生长情况。功能分析表明，dbpA在CRC组织和细胞系中过表达，高dbpA表达与浸润深度（p<0.001）、分化程度（p<0.001）、淋巴转移（p<0.001）和血管浸润（p<0.001）相关。抑制dbpA表达导致体外细胞增殖减少和体内肿瘤生长受抑，并诱导细胞周期停滞，促进CRC细胞凋亡。总体而言，我们的研究结果阐明了dbpA在结直肠癌发生中的关键作用。因此，dbpA可能作为CRC一种新的有效治疗靶点。
