[摘要] 目的：探究lncRNA HCG11 通过调控miR-144-3p 上调锌指蛋白E-盒结合同源异形盒-1（zine finger E box binding homeobox 1, ZEB1）基因的表达促进结直肠癌（colorectal cancer，CRC）发生及转移的分子机制。方法：收集2013 年1 月至2018 年1月云南省肿瘤医院结直肠外科手术切除的78 例CRC组织标本及其癌旁组织标本，采用qPCR检测HCG11 在CRC癌组织及细胞系中表达情况，以构建的HCG11 敲降载体、miR-144-3p 模拟物及抑制剂转染CRC细胞株SW480 及SW620，CCK-8 法及克隆形成实验检测细胞的增殖情况，Transwell 实验检测细胞的迁移及侵袭情况。通过Wb及免疫荧光实验检测ZEB1 及上皮间质特异蛋白（E-cadherin、Vimentin、ɑ-catenin、Sox2、Nestin、Oct4 及Nanog）的表达，通过双荧光素酶报告基因检测HCG11、miR-144-3p 及ZEB1 的靶向调控关系。建立小鼠移植瘤模型验证敲降HCG11 后对小鼠移植瘤生长的抑制作用。结果：HCG11 在CRC癌组织的表达显著高于癌旁组织（P<0.01），其在多种CRC细胞系中表达水平明显高于正常肠上皮细胞（均P<0.05）；HCG11 的表达与CRC患者肿瘤转移、临床分期及预后密切相关（P<0.05 或P<0.01）。敲降HCG11 后显著抑制CRC细胞的增殖、迁移、侵袭、上皮间质转化及干细胞转化（均P<0.05）。敲降HCG11 显著上调miR-144-3p 的表达水平（P<0.05），过表达miR-144-3p 可显著抑制ZEB1基因的表达（P<0.05）及明显降低双荧光素酶活性（P<0.05）。结论：HCG11 通过调控miR-144-3p 上调ZEB1 的表达，从而促进CRC的发生及转移，HCG11可作为CRC诊断及治疗的靶点。

[Abstract] Objective: To investigate the molecular mechanism of lncRNA-HCG11 promoting progression and metastasis of colorectal cancer (CRC) via up-regulating zinc finger E box binding homeobox 1 (ZEB1) by regulating miR-144-3p expression in CRC. Methods:A total of 78 pairs of CRC tissues and corresponding adjacent tissues were obtained from patients in Department of Colorectal Surgery,Cancer Hospital of Yunnan Province during January 2013 and January 2018. HCG11 expression level in CRC cell lines and tissues was determined by qPCR; HCG11-knockdown vector, miR-144-3p mimic and miR-144-3p inhibitor were constructed and transfected into CRC cells lines (SW480 and SW620); and then, cell viability was detected by using CCK-8 assay and colony formation assay,while cell migration and invasion was assessed by using transwell assay; the expression levels of ZEB1 and epithelial mesenchymal markers (E-cadherin, Vimentin, ɑ-catenin, Sox2, Nestin, Oct4 and Nanog) were detected by Wb and immunofluorescence assay; and the relationship between HCG11, miR-144-3p and ZEB1 was validated by dual-luciferase reporter gene assay. Nude mice xenograft model was constructed and the effect of HCG11 knock-down on the growth of xenograft was evaluated. Results: The expression of HCG11 was significantly higher in CRC cell lines (all P<0.05) and tissues (P<0.01) compared with that in normal colon epithelial cells and para-cancerous tissues; HCG11 expression was closely related with cancer metastasis, clinical staging and prognosis of CRC patients (all P<0.05). Knockdown of HCG11 significantly inhibited cells proliferation, migration, invasion, epithelial-mesenchymal transition and CRC stem cell formation (all P<0.05). Moreover, knockdown of HCG11 significantly up-regulated miR-144-3p expression (P<0.05),while over-expression of miR-144-3p significantly inhibited ZEB1 expression (P<0.05) and reduced dual-luciferase activity (P＜0.05).Conclusion: HCG11 regulates miR-144-3p to up-regulate ZEB1 expression, and further promotes CRC progression and metastasis;therefore, HCG11 could be used as a target for clinical diagnosis and treatment for CRC.