Background: Recently, microRNA-877-5p (miR-877) was recognized as a cancer-associated miRNA in hepatocellular and renal cell carcinomas. However, little is known regarding its expression pattern and role in colorectal cancer (CRC) tumorigenesis.
Material and methods: In the present study, reverse-transcription quantitative polymerase chain reaction was performed to detect miR-877 expression in CRC tissues and cell lines. A series of functional experiments were used to determine the effects of miR-877 upregulation on CRC cell proliferation, colony formation, apoptosis, migration, and invasion. In addition, the regulatory role of miR-877 in tumor growth was examined in vivo using a xenograft experiment. More importantly, the mechanisms underlying the action of miR-877 in CRC were explored.
Results: A significant decrease in the expression of miR-877 was observed in CRC tissues and cell lines. Low miR-877 expression correlated with lymph node metastasis and TNM stage of CRC patients. Functional experiments revealed that ectopic expression of miR-877 suppressed CRC cell proliferation and colony formation ability, induced cell apoptosis, inhibited cell migration and invasion in vitro, and reduced tumor growth in vivo. Metadherin (MTDH ) was recognized as a direct target of miR-877 in CRC cells. It was notably overexpressed in CRC tissues, and its expression was inversely correlated with that of miR-877 expression. Furthermore, MTDH  knockdown simulated the tumor suppressor activity of miR-877 in CRC cells. MTDH  restoration impaired the suppressive effects of miR-877 on malignant phenotypes of CRC cells. In addition, miR-877 inhibited the activation of the PTEN/Akt signaling pathway by regulating MTDH  expression both in vitro and in vivo.
Conclusion: Collectively, these results demonstrate that miR-877 inhibits the progression of CRC, at least partly by the direct targeting of MTDH  and regulation of the PTEN/Akt pathway. Thus, miR-877 may serve as a potential therapeutic target for the treatment of patients with CRC.
Keywords: microRNA-877, colorectal cancer, metadherin, PTEN/Akt pathway