Ye Jinjun, Liu Jidong, Tang Tao, Xin Le, Bao Xing, Yan Yukuang
Department of General Surgery, Shenzhen Longgang Central Hospital, No.6082 Longgang Avenue, Longgang District, Shenzhen, 518116, Guangdong, China.
Cancer Cell Int. 2021 Feb 3;21(1):87. doi: 10.1186/s12935-020-01706-w.
LINC00963 is high-expressed in various carcinomas, but its expression and function in colorectal cancer (CRC) have not been explored. This study explored the role and mechanism of LINC00963 in CRC.
The expression of LINC00963 in CRC and its relationship with prognosis were examined by starBase and survival analysis. The effects of LINC00963, miR-532-3p and HMGA2 on the biological characteristics and EMT-related genes of CRC cells were studied by RT-qPCR, CCK-8, clone formation experiments, flow cytometry, scratch test, Transwell, and Western blot. Xenograft assay and immunohistochemistry were performed to verify the effect of LINC00963 on tumor growth. The correlation among LINC00963, miR-532-3p, and HMGA2 was analyzed by bioinformatics analysis, luciferase assay, and Pearson test.
LINC00963 was high-expressed in CRC, and this was associated with poor prognosis of CRC. Silencing LINC00963 inhibited the activity, proliferation, migration, and invasion of CRC cells, MMP-3 and MMP-9 expressions, moreover, it also blocked cell cycle progression, and inhibited tumor growth and Ki67 expression. However, overexpression of LINC00963 showed the opposite effects to silencing LINC00963. LINC00963 targeted miR-532-3p to regulate HMGA2 expression. Down-regulation of miR-532-3p promoted cell proliferation, migration and invasion, and expressions of MMP-3 and MMP-9, and knockdown of HMGA2 reversed the effect of miR-532-3p inhibitor. Up-regulation of miR-532-3p inhibited the biological functions of CRC cells, and overexpression of HMGA2 reversed the miR-532-3p mimic effect.
LINC00963 affects the development of CRC through the miR-532-3p/HMGA2 axis.
LINC00963在多种癌症中高表达，但其在结直肠癌（CRC）中的表达及功能尚未得到研究。本研究探讨了LINC00963在CRC中的作用及机制。
通过starBase和生存分析检测LINC00963在CRC中的表达及其与预后的关系。采用RT-qPCR、CCK-8、克隆形成实验、流式细胞术、划痕试验、Transwell和蛋白质免疫印迹法研究LINC00963、miR-532-3p和HMGA2对CRC细胞生物学特性及上皮-间质转化（EMT）相关基因的影响。进行异种移植实验和免疫组织化学以验证LINC00963对肿瘤生长的影响。通过生物信息学分析、荧光素酶报告基因检测和Pearson检验分析LINC00963、miR-532-3p和HMGA2之间的相关性。
LINC00963在CRC中高表达，这与CRC的不良预后相关。沉默LINC00963可抑制CRC细胞的活性、增殖、迁移和侵袭，降低MMP-3和MMP-9的表达，此外，还可阻断细胞周期进程，抑制肿瘤生长和Ki67表达。然而，过表达LINC00963显示出与沉默LINC00963相反的作用。LINC00963靶向miR-532-3p以调节HMGA2的表达。下调miR-532-3p可促进细胞增殖、迁移和侵袭以及MMP-3和MMP-9的表达，敲低HMGA2可逆转miR-532-3p抑制剂的作用。上调miR-532-3p可抑制CRC细胞的生物学功能，过表达HMGA2可逆转miR-532-3p模拟物的作用。
LINC00963通过miR-532-3p/HMGA2轴影响CRC的发展。
