Research Papers:

MiR-520d-5p directly targets TWIST1 and downregulates the metastamiR miR-10b

Pinchas Tsukerman _, Rachel Yamin, Einat Seidel, Saleh Khawaled, Dominik Schmiedel, Tomer Bar-Mag and Ofer Mandelboim

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Oncotarget. 2014; 5:12141-12150. https://doi.org/10.18632/oncotarget.2559

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Pinchas Tsukerman1, Rachel Yamin1, Einat Seidel1, Saleh Khawaled1, Dominik Schmiedel1, Tomer Bar-Mag1, Ofer Mandelboim1

1The Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Israel Canada, Hadassah Medical School, Jerusalem, Israel

Correspondence to:

Ofer Mandelboim, e-mail: [email protected]

Keywords: TWIST1, miR-10b, mir-520d

Received: August 14, 2014     Accepted: October 01, 2014     Published: November 07, 2014


MicroRNAs are key players in most biological processes. Some microRNAs are involved in the genesis of tumors and are therefore termed oncomiRs, while others, termed metastamiRs, play a significant role in the formation of cancer metastases. Previously, we identified ten different cellular microRNAs that downregulate the expression of MICB, a ligand of the activating NK receptor NKG2D. Interestingly, several of the ten MICB-targeting microRNAs, such as miR-10b, are involved in tumor formation and metastasis. In this work, we identify a complex interplay between these different microRNAs. Specifically, we demonstrate that three of the MICB-targeting microRNAs: miR-20a, miR-17-5p and miR-93, also target the same site in the 3′UTR of TWIST1, a transcription factor implicated in cancer metastasis. Additionally, we show that miR-520d-5p targets a different site in the 3′UTR of TWIST1. We next show that the miR-520d-5p-mediated decrease of TWIST1 expression results in reduced expression of one of its targets, miR-10b, and in the restoration of E-Cadherin expression, which in turn results in reduced cellular motility and invasiveness. Finally, we show that miR-520d-5p leads to reduced proliferation of tumor cells, and that high levels of miR-520d-5p correlate with higher survival rates of cancer patients.

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