MiR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis

X. Fu, Z. Meng, W. Liang, Y. Tian, X. Wang, W. Han, G. Lou, X. Wang, F. Lou, Y. Yen, H. Yu, R. Jove, W. Huang

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Human cancers often exhibit attenuated microRNA (miRNA) biogenesis and global underexpression of miRNAs; thus, targeting the miRNA biogenesis pathway represents a novel strategy for cancer therapy. Here, we report that miR-26a enhances miRNA biogenesis, which acts as a common mechanism partially accounting for miR-26a function in diverse cancers including melanoma, prostate and liver cancer. miR-26a was broadly reduced in multiple cancers, and overexpression of miR-26a significantly suppressed tumor growth and metastasis both in vitro and in vivo, including melanoma, prostate and liver cancers. Notably, miR-26a overexpression was accompanied by global upregulation of miRNAs, especially let-7, and let-7 expression was concordant with miR-26a expression in cancer cell lines, xenograft tumors and normal human tissues, underscoring their biological relevance. We showed that miR-26a directly targeted Lin28B and Zcchc11 - two critical repressors of let-7 maturation. Furthermore, we have demonstrated that Zcchc11 promoted tumor growth and metastasis, and it was prominently overexpressed in human cancers. Our findings thus provide a novel mechanism by which a miRNA acts as a modulator of miRNA biogenesis. These results also define a role of the miR-26a and Zcchc11 in tumorigenesis and metastasis and have implications to develop new strategies for cancer therapy.

Original languageEnglish
Pages (from-to)4296-4306
Number of pages11
JournalOncogene
Volume33
Issue number34
DOIs
Publication statusPublished - Aug 21 2014
Externally publishedYes

Fingerprint

MicroRNAs
Neoplasm Metastasis
Growth
Neoplasms
Liver Neoplasms
Melanoma
Prostatic Neoplasms
Tumor Cell Line
Heterografts
Carcinogenesis
Up-Regulation
Therapeutics

Keywords

  • let-7
  • metastasis
  • miR-26a
  • miRNA biogenesis
  • tumorigenesis
  • Zcchc11

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Fu, X., Meng, Z., Liang, W., Tian, Y., Wang, X., Han, W., ... Huang, W. (2014). MiR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis. Oncogene, 33(34), 4296-4306. https://doi.org/10.1038/onc.2013.385

MiR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis. / Fu, X.; Meng, Z.; Liang, W.; Tian, Y.; Wang, X.; Han, W.; Lou, G.; Wang, X.; Lou, F.; Yen, Y.; Yu, H.; Jove, R.; Huang, W.

In: Oncogene, Vol. 33, No. 34, 21.08.2014, p. 4296-4306.

Research output: Contribution to journalArticle

Fu, X, Meng, Z, Liang, W, Tian, Y, Wang, X, Han, W, Lou, G, Wang, X, Lou, F, Yen, Y, Yu, H, Jove, R & Huang, W 2014, 'MiR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis', Oncogene, vol. 33, no. 34, pp. 4296-4306. https://doi.org/10.1038/onc.2013.385
Fu, X. ; Meng, Z. ; Liang, W. ; Tian, Y. ; Wang, X. ; Han, W. ; Lou, G. ; Wang, X. ; Lou, F. ; Yen, Y. ; Yu, H. ; Jove, R. ; Huang, W. / MiR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis. In: Oncogene. 2014 ; Vol. 33, No. 34. pp. 4296-4306.
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