Solute carrier organic anion transporter family member 4A1 promotes colorectal cancer progression and is regulated by miR-1224-5p

Yan Jiang, Xizhen Zhou, Yingying Li,  Xiaojie Gao

Abstract:

Colorectal cancer (CRC) is one of the most common malignant tumors, and pharmacological treatments of CRC are unsatisfactory. Increasing evidence shows that solute carrier organic anion transporter family member 4A1 (SLCO4A1) is abnormally expressed in numerous cancer types and may be correlated with cancer development and metastasis. However, the roles of SLCO4A1 in CRC are incompletely understood. This study utilized the GSE110224 dataset and other databases to analyze SLCO4A1 expression levels in CRC tissues. The expression levels of SLCO4A1 in CRC cell lines were evaluated by quantitative real-time polymerase chain reaction and western blotting. The roles of SLCO4A1 in CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition were assessed. The interaction between SLCO4A1 and microRNA-1224-5p was verified using a dual-luciferase reporter assay. The effect of SLCO4A1 in vivo was investigated using a BALB/c mouse model. The level of SLCO4A1 expression was increased in CRC tissues and cell lines. Moreover, high SLCO4A1 expression was positively associated with a poor prognosis. The results of gain- and loss-of-function experiments showed that SLCO4A1 knockdown suppressed CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition while SLCO4A1 overexpression had opposite effects in vitro. Furthermore, SLCO4A1 knockdown could suppress tumor growth in vivo. Further analyses showed that SLCO4A1 was downregulated by miR-1224-5p. Rescue experiments confirmed that SLCO4A1 reversed the effect of miR-1224-5p on cell function. These results suggested that SLCO4A1 acted as an oncogene to regulate CRC development and was a potential target for CRC treatment.