| Emerging evidence has implicated long non-coding RNAs (lncRNAs) as master gene regulators, and they are often aberrantly expressed in a variety of human diseases including cancer. One of the mechanisms of 1ncRNA-mediated gene expression involves modulation of translation or mRNA stability by interacting with RNA binding proteins. We have previously demonstrated that 1ncRNA regulator of reprogramming (RoR) is a strong negative regulator of p53 in response to DNA damage. We present evidence that RoR plays an oncogenic role in colon cancer progression. We have first shown RoR is upregulated in colon cancer tissues and induces tumor growth. We also identified that ectopic expression of RoR induces, knockdown of RoR by siRNA reduces c-Myc mRNA and protein levels independent of p53 or miR-145 pathway. To further study the effect of RoR on c-Myc, we generated RoR knockout (KO) HCT116 cells by applying CRISPR/Cas9 system. Proliferation rate and c-Myc mRNA stability are significantly reduced in two RoR KO cells. Furthermore, we demonstrated that RoR induces c-Myc mRNA stability by competitively binding with AU-rich element binding protein (AUF1) and facilitating heterogeneous nuclear ribonucleoprotein I (hnRNP I) binding with c-Myc mRNA. In addition, as a RNA binding protein, hnRNP I has been involved in diverse diseases, including cancer. We also identified that hnRNP I can functionally interact with urothelial carcinoma-associated 1 (UCA1) in addition to RoR. Phosphorylation of hnRNP I stabilizes UCA1 which is upregulated in breast cancer specimens. Upregulation of UCA1 induces breast cancer proliferation by inhibiting p27 translation. Furthermore, UCA1 represses p27 translation by competitively binding with hnRNP I. In conclusion, we suggest that both RoR and UCA1 play oncogenic roles in cancer. |
