LncRNA-HCG11 affects progression and metastasis of colorectal cancer via regulating miR-144-3p/ZEB1 axis / 中国肿瘤生物治疗杂志

ABSTRACT

@#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:Atotal 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.