OncoTargets and Therapy (Dec 2019)

MicroRNA-145 Inhibits Cell Migration and Invasion in Colorectal Cancer by Targeting TWIST

  • Shen X,
  • Jiang H,
  • Chen Z,
  • Lu B,
  • Zhu Y,
  • Mao J,
  • Chai K,
  • Chen W

Journal volume & issue
Vol. Volume 12
pp. 10799 – 10809

Abstract

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Xuning Shen,1 Honggang Jiang,1 Zhiheng Chen,1 Bohao Lu,1 Yi Zhu,1 Jiayan Mao,2 Kequn Chai,2,3 Wei Chen2,3 1Department of Gastroenterological Surgery, Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 2Cancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang 310012, People’s Republic of China; 3Department of Medical Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, People’s Republic of ChinaCorrespondence: Wei Chen; Kequn ChaiCancer Institute of Integrated Traditional Chinese and Western Medicine, Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang 310012, People’s Republic of ChinaTel +86-571-89972114Fax +86 571-88853199Email [email protected]; [email protected]: MicroRNAs function as oncogenes or tumor suppressors in the development of various human cancers. We investigated the effect of microRNA-145 (miR-145) on colorectal cancer (CRC) cell invasion and migration.Methods: The levels of miR-145 in CRC cells were examined by quantitative PCR; Western blotting was used to detect TWIST1 (twist family bHLH transcription factor 1) protein and the epithelial–mesenchymal transition (EMT)-related proteins (E-cadherin, vimentin). Then, we transfected miR-145 mimics or inhibitor into CRC cells and used the wound healing and Transwell invasion assays to investigate their migration and invasive capability, respectively.Results: The miR-145 mimics suppressed CRC cell invasion and migration significantly; in contrast, miR-145 downregulation had the opposite effect. Furthermore, miR-145 regulated TWIST1 levels negatively at transcriptional level. TWIST1 knockdown significantly inhibited the CRC cell migration ability and the number of CRC cells that crossed the Transwell membrane. There was no significant difference in terms of migration and invasive capability after the cells had been transfected with miR-145 mimics or inhibitor plus TWIST1 small interfering RNA (siRNA) as compared to the TWIST1 siRNA–only group. Furthermore, we demonstrate that the inhibition of miR-145 could enhance the capability for lung metastasis in vivo.Conclusion: Taken together, these findings indicate that miR-145 acts as a new tumor suppressor by regulating TWIST1 and plays a vital role in the invasive and migration ability of CRC cells.Keywords: MicroRNA-145, cell migration and invasion, colorectal cancer, TWIST, EMT

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