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 language | English |
|---|---|
| Pages (from-to) | 4296-4306 |
| Number of pages | 11 |
| Journal | Oncogene |
| Volume | 33 |
| Issue number | 34 |
| DOIs | |
| Publication status | Published - Aug 21 2014 |
| Externally published | Yes |
Fingerprint
Keywords
- let-7
- metastasis
- miR-26a
- miRNA biogenesis
- tumorigenesis
- Zcchc11
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - MiR-26a enhances miRNA biogenesis by targeting Lin28B and Zcchc11 to suppress tumor growth and metastasis
AU - Fu, X.
AU - Meng, Z.
AU - Liang, W.
AU - Tian, Y.
AU - Wang, X.
AU - Han, W.
AU - Lou, G.
AU - Wang, X.
AU - Lou, F.
AU - Yen, Y.
AU - Yu, H.
AU - Jove, R.
AU - Huang, W.
PY - 2014/8/21
Y1 - 2014/8/21
N2 - 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.
AB - 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.
KW - let-7
KW - metastasis
KW - miR-26a
KW - miRNA biogenesis
KW - tumorigenesis
KW - Zcchc11
UR - http://www.scopus.com/inward/record.url?scp=84906936211&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906936211&partnerID=8YFLogxK
U2 - 10.1038/onc.2013.385
DO - 10.1038/onc.2013.385
M3 - Article
C2 - 24056962
AN - SCOPUS:84906936211
VL - 33
SP - 4296
EP - 4306
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 34
ER -