Abstract
Increasing evidence suggest that lncRNAs (long noncoding RNAs) play important roles in human cancer. Breast cancer is a heterogeneous disease and the potential involvement of lncRNAs in breast cancer remains unexplored. In this study, we characterized a novel lncRNA, RP1-5O6.5 (termed as RP1). We found that RP1 was highly expressed in breast cancer and predicted poor prognosis of breast cancer patients. Gain-of-function and loss-of-function assays showed that RP1 promoted the proliferation and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, RP1 maintained the EMT and stemness states of breast cancer cells via repressing p27kip1 protein expression. RP1 combined with the complex p-4E-BP1/eIF4E to prevent eIF4E from interacting with eIF4G, therefore attenuating the translational efficiency of p27kip1 mRNA. Furthermore, we found that p27kip1 evidently downregulated Snail1 but not ZEB1 to inhibit invasion of breast cancer cells. Kruppel-like factor 5 (KLF5) was positively correlated with RP1 in breast cancer tissues. Moreover, we demonstrated that KLF5 recruited p300 to the RP1 promoter to enhance RP1 expression. Taken together, our findings demonstrated that KLF5-regulated RP1 plays an oncogenic role in breast cancer by suppressing p27kip1, providing support for the clinical investigation of therapeutic approaches focusing on RP1.
Highlights
Breast cancer is still the most malignant female tumor in the world
We found that RP1 expression was especially elevated in the triplenegative breast cancer (TNBC) cohort in comparison with cohorts of luminal A, luminal B, and HER2+ breast cancer (Fig. 1b)
We found that RP1 expression was positively correlated with tumor size, node status, TNM stage, and distant metastasis (Table S1)
Summary
Breast cancer is still the most malignant female tumor in the world. It has been estimated that about 249,260 new cases and 40,890 deaths from breast cancer occurred in the United States in 20161. In China, it is estimated that approximately 272,400 new cases and 70,700 deaths from breast cancer in occurred in 20152. Breast cancer is a heterogeneous disease having a variety of histopathological features, genetic markers, and diverse prognostic outcomes. Breast cancer can be divided basing on gene. Accumulating evidence has indicated that long noncoding RNAs (lncRNAs) play a significant role in breast cancer[5]. The transcript sizes of lncRNAs are over 200 bp and up to 100 kb, as the name implies they are non-coding[6]. Dysregulation of lncRNAs contributes to the development and progression
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