Cancer Management and Research (Apr 2019)

microRNA-877 inhibits malignant progression of colorectal cancer by directly targeting MTDH and regulating the PTEN/Akt pathway

  • Zhang L,
  • Li C,
  • Cao L,
  • Li H,
  • Zou H,
  • Li H,
  • Pei H

Journal volume & issue
Vol. Volume 11
pp. 2769 – 2781

Abstract

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Lunqiang Zhang,1 Chenglong Li,1 Lijun Cao,2 Hui Li,2 Haiding Zou,2 Hongqin Li,2 Haiping Pei11Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Hunan 410008, People’s Republic of China; 2Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Hunan 410011, People’s Republic of ChinaBackground: 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  

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