A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

Pengpeng Zhu, Fang He, Yixuan Hou, Gang Tu, Qiao Li, Ting Jin, Huan Zeng, Yilu Qin, Xueying Wan, Yina Qiao, Yuxiang Qiu, Yong Teng, Manran Liu

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

Original languageEnglish (US)
Pages (from-to)1609-1627
Number of pages19
JournalOncogene
Volume40
Issue number9
DOIs
StatePublished - Mar 4 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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