Song Xiaobin, Li Longjie, Shi Liang, Liu Xinyu, Qu Xun, Wei Fengcai, Wang Ketao
Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China.
Institute of Stomatology, Shandong University, Jinan, 250012, China.
Cancer Cell Int. 2021 Dec 14;21(1):666. doi: 10.1186/s12935-021-02377-x.
C1QTNF6 (CTRP6), a member of the CTRP family, has recently been implied to play a role in the tumorigenesis of for a variety of cancer types. However, the role of C1QTNF6 in oral squamous cell carcinoma (OSCC) and its potential molecular remains unclear.
C1QTNF6 expression was detected by qRT-PCR and western blot analysis. Lentiviral vectors were constructed to knockdown C1QTNF6 in CaL27 and SCC-9 human OSCC cell lines. Cell viability, cell cycle and cell apoptosis analyses were performed by MTT assay, PI/Annexin V staining, and flow cytometry. The effect of C1QTNF6 knockdown on in vivo tumorigenicity of OSCC cells in vivo was evaluated using nude mouse xenograft tumor model. Downstream signaling mechanisms were identified by microarray and Ingenuity Pathway Analysis.
Immunohistochemistry of OSCC tissue and data from TCGA demonstrate that C1QTNF6 was overexpressed in OSCC tissues, and that cellular proliferation was significantly decreased after C1QTNF6 was knockdown in CaL27 and SCC-9 cell lines. Knockdown of C1QTNF6 also resulted in cell cycle arrest at the G2/M phase and enhanced cell apoptosis in in CaL27 and SCC-9 cell lines. Furthermore, knockdown of C1QTNF6 in Cal-27 cells inhibited tumor growth of OSCC in vivo. Microarray analysis revealed that C1QTNF6 silencing resulted in significant alterations of gene expression, with the Acute Phase Response signaling pathway significantly activated following C1QTNF6 silencing.
These results suggest that C1QTNF6 plays an important role in promoting OSCC tumorigenesis, which indicates that C1QTNF6 may comprise a promising therapeutic target for OSCC treatment.
C1QTNF6（CTRP6）是CTRP家族的成员，最近被认为在多种癌症类型的肿瘤发生中起作用。然而，C1QTNF6在口腔鳞状细胞癌（OSCC）中的作用及其潜在分子机制仍不清楚。
通过qRT-PCR和蛋白质免疫印迹分析检测C1QTNF6的表达。构建慢病毒载体以敲低CaL27和SCC-9人OSCC细胞系中的C1QTNF6。通过MTT法、PI/Annexin V染色和流式细胞术进行细胞活力、细胞周期和细胞凋亡分析。使用裸鼠异种移植肿瘤模型评估敲低C1QTNF6对OSCC细胞体内致瘤性的影响。通过微阵列和 Ingenuity 通路分析确定下游信号传导机制。
OSCC组织的免疫组织化学和来自TCGA的数据表明，C1QTNF6在OSCC组织中过表达，并且在CaL27和SCC-9细胞系中敲低C1QTNF6后细胞增殖显著降低。敲低C1QTNF6还导致CaL27和SCC-9细胞系中的细胞周期停滞在G2/M期并增强细胞凋亡。此外，在Cal-27细胞中敲低C1QTNF6可抑制OSCC在体内的肿瘤生长。微阵列分析显示，C1QTNF6沉默导致基因表达的显著改变，C1QTNF6沉默后急性期反应信号通路被显著激活。
这些结果表明C1QTNF6在促进OSCC肿瘤发生中起重要作用，这表明C1QTNF6可能是OSCC治疗的一个有前景的治疗靶点。
