Abstract
The oncoprotein c-Myc is essential for cell growth and proliferation while its deregulated overexpression is associated with most human cancers. Thus tightly regulated levels and activity of c-Myc are critical for maintaining normal cell homeostasis. c-Myc is down-regulated in response to several types of stress, including UV-induced DNA damage. Yet, mechanism underlying UV-induced c-Myc reduction is not completely understood. Here we report that L11 promotes miR-130a targeting of c-myc mRNA to repress c-Myc expression in response to UV irradiation. miR-130a targets the 3'-untranslated region (UTR) of c-myc mRNA. Overexpression of miR-130a promotes the Ago2 binding to c-myc mRNA, significantly reduces the levels of both c-Myc protein and mRNA and inhibits cell proliferation. UV treatment markedly promotes the binding of L11 to miR-130a, c-myc mRNA as well as Ago2 in cells. Inhibiting miR-130a significantly suppresses UV-mediated c-Myc reduction. We further show that L11 is relocalized from the nucleolus to the cytoplasm where it associates with c-myc mRNA upon UV treatment. Together, these results reveal a novel mechanism underlying c-Myc down-regulation in response to UV-mediated DNA damage, wherein L11 promotes miR-130a-loaded miRISC to target c-myc mRNA.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1101-1114 |
| Number of pages | 14 |
| Journal | Oncotarget |
| Volume | 6 |
| Issue number | 2 |
| State | Published - 2015 |
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Keywords
- C-Myc
- L11
- MicroRNA
- miR-130a
- UV irradiation
ASJC Scopus subject areas
- Oncology
Cite this
MicroRNA-130a associates with ribosomal protein L11 to suppress c-Myc expression in response to UV irradiation. / Li, Yuhuang; Challagundla, Kishore B.; Sun, Xiao-Xin; Zhang, Qinghong; Dai, Mushui.
In: Oncotarget, Vol. 6, No. 2, 2015, p. 1101-1114.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA-130a associates with ribosomal protein L11 to suppress c-Myc expression in response to UV irradiation
AU - Li, Yuhuang
AU - Challagundla, Kishore B.
AU - Sun, Xiao-Xin
AU - Zhang, Qinghong
AU - Dai, Mushui
PY - 2015
Y1 - 2015
N2 - The oncoprotein c-Myc is essential for cell growth and proliferation while its deregulated overexpression is associated with most human cancers. Thus tightly regulated levels and activity of c-Myc are critical for maintaining normal cell homeostasis. c-Myc is down-regulated in response to several types of stress, including UV-induced DNA damage. Yet, mechanism underlying UV-induced c-Myc reduction is not completely understood. Here we report that L11 promotes miR-130a targeting of c-myc mRNA to repress c-Myc expression in response to UV irradiation. miR-130a targets the 3'-untranslated region (UTR) of c-myc mRNA. Overexpression of miR-130a promotes the Ago2 binding to c-myc mRNA, significantly reduces the levels of both c-Myc protein and mRNA and inhibits cell proliferation. UV treatment markedly promotes the binding of L11 to miR-130a, c-myc mRNA as well as Ago2 in cells. Inhibiting miR-130a significantly suppresses UV-mediated c-Myc reduction. We further show that L11 is relocalized from the nucleolus to the cytoplasm where it associates with c-myc mRNA upon UV treatment. Together, these results reveal a novel mechanism underlying c-Myc down-regulation in response to UV-mediated DNA damage, wherein L11 promotes miR-130a-loaded miRISC to target c-myc mRNA.
AB - The oncoprotein c-Myc is essential for cell growth and proliferation while its deregulated overexpression is associated with most human cancers. Thus tightly regulated levels and activity of c-Myc are critical for maintaining normal cell homeostasis. c-Myc is down-regulated in response to several types of stress, including UV-induced DNA damage. Yet, mechanism underlying UV-induced c-Myc reduction is not completely understood. Here we report that L11 promotes miR-130a targeting of c-myc mRNA to repress c-Myc expression in response to UV irradiation. miR-130a targets the 3'-untranslated region (UTR) of c-myc mRNA. Overexpression of miR-130a promotes the Ago2 binding to c-myc mRNA, significantly reduces the levels of both c-Myc protein and mRNA and inhibits cell proliferation. UV treatment markedly promotes the binding of L11 to miR-130a, c-myc mRNA as well as Ago2 in cells. Inhibiting miR-130a significantly suppresses UV-mediated c-Myc reduction. We further show that L11 is relocalized from the nucleolus to the cytoplasm where it associates with c-myc mRNA upon UV treatment. Together, these results reveal a novel mechanism underlying c-Myc down-regulation in response to UV-mediated DNA damage, wherein L11 promotes miR-130a-loaded miRISC to target c-myc mRNA.
KW - C-Myc
KW - L11
KW - MicroRNA
KW - miR-130a
KW - UV irradiation
UR - http://www.scopus.com/inward/record.url?scp=84921759798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921759798&partnerID=8YFLogxK
M3 - Article
C2 - 25544755
AN - SCOPUS:84921759798
VL - 6
SP - 1101
EP - 1114
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 2
ER -