Circ_0000218 plays a carcinogenic role in colorectal cancer progression by regulating miR-139-3p/RAB1A axis

• Published in: Journal of biochemistry (Tokyo) Vol. 167; no. 1; pp. 55 - 65
• Main Authors: Pei, Fu-Lai, Cao, Ming-Zheng, Li, Yue-Feng
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-01-2020
• Subjects: Carcinogenesis - genetics; Cell Movement; Cell Proliferation; Cells, Cultured; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; rab1 GTP-Binding Proteins - genetics; rab1 GTP-Binding Proteins - metabolism; RNA, Circular - genetics; RNA, Circular - metabolism; circ_0000218; RAB1A; miR-139-3p; CRC
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvz078

Abstract
Accumulating researches have confirmed that circRNA abnormal expression plays a prominent role in the progression of colorectal cancer (CRC). The role of circ_0000218 in CRC and its potential mechanism are not clear. In this study, real-time polymerase chain reaction (RT-PCR) was employed to measure the circ_0000218, miR-139-3p and RAB1A mRNA expression in CRC tissues and cells. Immunohistochemistry and western blot were conducted to determine the RAB1A expression in CRC tissues and cells, respectively. Colony formation assay and BrdU method were employed to monitor the effect of circ_0000218 on cell proliferation. Transwell assay was adopted to detect cell migration and invasion. Dual luciferase reporter assay and RNA immunoprecipitation assay were adopted to confirm the targeting relationship between circ_0000218 and miR-139-3p, miR-139-3p and RAB1A. We demonstrated that circ_0000218 was notably upregulated in CRC tissues and cell lines, and its high expression level was markedly linked to the increase of T staging and local lymph node metastasis. Circ_0000218 overexpression enhanced the proliferation and metastasis of CRC cells while knocking down circ_0000218 caused the opposite effects. We also observed that miR-139-3p was negatively regulated by circ_0000218, while RAB1A was positively regulated by it. Collectively, this study suggested that circ_0000218 upregulated RAB1A and promoted CRC proliferation and metastasis via sponging miR-139-3p.