Abstract：
BACKGROUND: Aberrant expression of collagen type V alpha 1 chain (COL5A1) has been linked to several forms of human cancers. In this work, we focused on the interaction of the LINC00173/GATA binding protein 6 (GATA6)/COL5A1 axis in the malignant property of oral squamous cell carcinoma (OSCC) cells.
METHODS: We analyzed six publicly accessible datasets GSE160042, GSE74530, GSE138206, GSE23558, GSE31853 and GSE146483 to identify aberrantly expressed genes in OSCC. The expression of COL5A1 in OSCC tissues and cell lines was examined by reverse transcription-quantitative polymerase chain reaction and/or immunohistochemistry. The regulatory mechanism responsible for COL5A1 transcription was predicted via bioinformatics systems, and the interactions of LINC00173, GATA6, and COL5A1 were identified by immunoprecipitation and luciferase assays. Overexpression or downregulation of COL5A1, GATA6, and LINC00173 were induced in OSCC cell lines to determine their roles in the malignant phenotype of the OSCC cells in vitro and in vivo.
RESULTS: COL5A1 showed elevated expression in OSCC tissues and cells. The COLA51 knockdown suppressed proliferation, migration and invasiveness, apoptosis resistance, and pro-angiogenic ability of OSCC cells, and it suppressed the growth and dissemination of xenograft tumors in vivo. GATA6 bound to COL5A1 promoter to activate its transcription, whereas LINC00173 bound to GATA6 to block this transcriptional activation. Overexpression of GATA6 or COL5A1 promoted the malignant phenotype of the OSCC cells, which were blocked upon LINC00173 upregulation.
CONCLUSIONS: This work demonstrates that LINC00173 blocks GATA6-mediated transcription of COL5A1 to affect malignant development of OSCC.
METHODS: We analyzed six publicly accessible datasets GSE160042, GSE74530, GSE138206, GSE23558, GSE31853 and GSE146483 to identify aberrantly expressed genes in OSCC. The expression of COL5A1 in OSCC tissues and cell lines was examined by reverse transcription-quantitative polymerase chain reaction and/or immunohistochemistry. The regulatory mechanism responsible for COL5A1 transcription was predicted via bioinformatics systems, and the interactions of LINC00173, GATA6, and COL5A1 were identified by immunoprecipitation and luciferase assays. Overexpression or downregulation of COL5A1, GATA6, and LINC00173 were induced in OSCC cell lines to determine their roles in the malignant phenotype of the OSCC cells in vitro and in vivo.
RESULTS: COL5A1 showed elevated expression in OSCC tissues and cells. The COLA51 knockdown suppressed proliferation, migration and invasiveness, apoptosis resistance, and pro-angiogenic ability of OSCC cells, and it suppressed the growth and dissemination of xenograft tumors in vivo. GATA6 bound to COL5A1 promoter to activate its transcription, whereas LINC00173 bound to GATA6 to block this transcriptional activation. Overexpression of GATA6 or COL5A1 promoted the malignant phenotype of the OSCC cells, which were blocked upon LINC00173 upregulation.
CONCLUSIONS: This work demonstrates that LINC00173 blocks GATA6-mediated transcription of COL5A1 to affect malignant development of OSCC.
摘要：
背景：V型胶原α1链（COL5A1）的异常表达与几种形式的人类癌症有关。在这项工作中,我们专注于LINC00173/GATA结合蛋白6（GATA6）/COL5A1轴在口腔鳞状细胞癌（OSCC）细胞恶性特性中的相互作用。
方法：我们分析了六个可公开访问的数据集GSE160042、GSE74530、GSE138206、GSE23558、GSE31853和GSE146483，以鉴定OSCC中异常表达的基因。通过RT-qPCR和/或免疫组织化学检查OSCC组织和细胞系中COL5A1的表达。通过生物信息学系统预测了负责COL5A1转录的调控机制，通过免疫沉淀和荧光素酶测定鉴定了LINC00173，GATA6和COL5A1的相互作用。在OSCC细胞系中诱导COL5A1，GATA6和LINC00173的过表达或下调，以确定它们在体外和体内OSCC细胞恶性表型中的作用。
结果：COL5A1在OSCC组织和细胞中表达升高。COLA51敲除抑制了增殖，移民和入侵，凋亡抗性，和OSCC细胞的促血管生成能力，它抑制了体内异种移植肿瘤的生长和扩散。GATA6与COL5A1启动子结合以激活其转录，而LINC00173与GATA6结合以阻断这种转录激活。GATA6或COL5A1的过表达促进了OSCC细胞的恶性表型，LINC00173上调后被阻断。
结论：这项工作表明LINC00173阻断GATA6介导的COL5A1转录以影响OSCC的恶性发展。
方法：我们分析了六个可公开访问的数据集GSE160042、GSE74530、GSE138206、GSE23558、GSE31853和GSE146483，以鉴定OSCC中异常表达的基因。通过RT-qPCR和/或免疫组织化学检查OSCC组织和细胞系中COL5A1的表达。通过生物信息学系统预测了负责COL5A1转录的调控机制，通过免疫沉淀和荧光素酶测定鉴定了LINC00173，GATA6和COL5A1的相互作用。在OSCC细胞系中诱导COL5A1，GATA6和LINC00173的过表达或下调，以确定它们在体外和体内OSCC细胞恶性表型中的作用。
结果：COL5A1在OSCC组织和细胞中表达升高。COLA51敲除抑制了增殖，移民和入侵，凋亡抗性，和OSCC细胞的促血管生成能力，它抑制了体内异种移植肿瘤的生长和扩散。GATA6与COL5A1启动子结合以激活其转录，而LINC00173与GATA6结合以阻断这种转录激活。GATA6或COL5A1的过表达促进了OSCC细胞的恶性表型，LINC00173上调后被阻断。
结论：这项工作表明LINC00173阻断GATA6介导的COL5A1转录以影响OSCC的恶性发展。
