miR‐140‐3p inhibits colorectal cancer progression and its liver metastasis by targeting BCL9 and BCL2

Abstract

Abstract Recent studies have identified microRNAs (miRNAs) as a compelling novel class of biomarker in colorectal cancer (CRC) development and metastasis. Here, we demonstrated that the level of plasma exosomal miR‐140‐3p in CRC patients was lower than that in healthy controls. The decreased miR‐140‐3p level was also observed in CRC patients with liver metastasis. The expression of miR‐140‐3p in CRC tissues were significantly lower than that in matched normal tissues. Functionally, miR‐140‐3p overexpression suppressed proliferation, migration, invasion, and β‐catenin nuclear translocation, as well as promoted apoptosis in LoVo cells, while inhibition of miR‐140‐3p reversed these cellular processes in HCT 116 cells. Notably, BCL9 and BCL2 were recognized as direct targets of miR‐140‐3p. BCL9 knockdown abrogated miR‐140‐3p inhibitor‐induced effects on HCT 116 cells with decreased proliferation, migration, and invasion. BCL2 knockdown increased apoptosis of miR‐140‐3p inhibitor‐transfected HCT 116 cells. In vivo experiments revealed that miR‐140‐3p overexpression inhibited tumor growth in LoVo xenograft model and diminished metastatic nodules in nude mice liver. Taken together, this work supports that miR‐140‐3p exerts as a tumor suppressor in CRC progression via targeting BCL9 and BCL2, and suggests miR‐140‐3p‐BCL9/BCL2 axis may be applied in miRNA‐based therapy and prognostication of CRC.

Keywords

• BCL2
• BCL9
• colorectal cancer
• metastasis
• miR‐140‐3p