MicroRNA-130a associates with ribosomal protein L11 to suppress c-Myc expression in response to UV irradiation

Yuhuang Li, Kishore B. Challagundla, Xiao-Xin Sun, Qinghong Zhang, Mushui Dai

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1101-1114
Number of pages14
JournalOncotarget
Volume6
Issue number2
StatePublished - 2015

Fingerprint

MicroRNAs
Messenger RNA
DNA Damage
Cell Proliferation
Proto-Oncogene Proteins c-myc
Oncogene Proteins
3' Untranslated Regions
ribosomal protein L11
Cytoplasm
Homeostasis
Down-Regulation
Growth
Neoplasms

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 journalArticle

Li, Yuhuang ; Challagundla, Kishore B. ; Sun, Xiao-Xin ; Zhang, Qinghong ; Dai, Mushui. / MicroRNA-130a associates with ribosomal protein L11 to suppress c-Myc expression in response to UV irradiation. In: Oncotarget. 2015 ; Vol. 6, No. 2. pp. 1101-1114.
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