Podocalyxin-like, targeted by miR-138, promotes colorectal cancer cell proliferation, migration, invasion and EMT.

ABSTRACT

OBJECTIVE: Emerging evidence has shown that Podocalyxin-like (PODXL) plays an important role in the development and progression of several tumors, including colorectal cancer (CRC). However, its potential role in CRC is still not documented. The present study aimed to explore biological functions and molecular mechanisms in CRC development. PATIENTS AND METHODS: Microarray data were downloaded from TCGA datasets and statistically analyzed. RT-PCR was performed to detect the expression of PODXL and miR-138. Lost-function assay was used to explore the roles of PODXL on CRC behavior. Bioinformatics tools were used to identify the upstream miRNAs and the relationship between PODXL and miR-138 was detected via Dual-Luciferase assay, Western blot and rescue experiments. RESULTS: PODXL expression was significantly up-regulated in both CRC tissues and cell lines. In vitro experiments showed the knockdown of PODXL suppressed reduces CRC tumor growth, metastasis and EMT, and promoted apoptosis. Moreover, PODXL was predicted and confirmed to be a target of miR-138. In addition, ectopic expression of PODXL significantly reversed the suppression of cell proliferation and metastasis caused by the miR-138 over-expression. CONCLUSIONS: We provided important evidence that PODXL, targeted by miR-138, acted as a tumor promoter in CRC by suppressing CRC cells proliferation and metastasis, which may provide a novel potential target for diagnostic and therapeutic applications in CRC.