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

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

Received 9 November 2018

Accepted for publication 15 February 2019

Published 8 April 2019 Volume 2019:11 Pages 2769—2781

DOI https://doi.org/10.2147/CMAR.S194073

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 3

Editor who approved publication: Dr Ahmet Emre Eskazan


Lunqiang Zhang,1 Chenglong Li,1 Lijun Cao,2 Hui Li,2 Haiding Zou,2 Hongqin Li,2 Haiping Pei1

1Department 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 China

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
 

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