Abstract
Triple-negative breast cancer (TNBC) exhibits poor prognosis, with high metastasis and low survival. Long non-coding RNAs (lncRNAs) play critical roles in tumor progression. Here, we identified lncRNA MIR100HG as a pro-oncogene for TNBC progression. Knockdown of MIR100HG decreased cell proliferation and induced cell arrest in the G1 phase, whereas overexpression of MIR100HG significantly increased cell proliferation. Furthermore, MIR100HG regulated the p27 gene to control the cell cycle, and subsequently impacted the progression of TNBC. In analyzing its underlying mechanism, bioinformatics prediction and experimental data demonstrated that MIR100HG participated in the formation of RNA–DNA triplex structures. MIR100HG in The Cancer Genome Atlas (TCGA) and breast cancer cell lines showed higher expression in TNBC than in other tumor types with poor prognosis. In conclusion, our data indicated a novel working pattern of lncRNA in TNBC progression, which may be a potential therapeutic target in such cancers.
Highlights
Breast cancer is a molecularly-heterogeneous disease and can be classified into four molecular subtypes, including luminal A, luminal B, human epidermal growth factor receptor type 2 (HER2) positive, and triple-negative breast cancer (TNBC)[1,2]
We showed that MIR100HG was more highly expressed in poor prognosis TNBC compared with other breast cancer subtypes
We found that MIR100HG regulated p27 through the formation of an RNA–DNA triplex structure, providing a new avenue for Long non-coding RNAs (lncRNAs) studies
Summary
Breast cancer is a molecularly-heterogeneous disease and can be classified into four molecular subtypes, including luminal A, luminal B, human epidermal growth factor receptor type 2 (HER2) positive, and triple-negative breast cancer (TNBC)[1,2]. TNBC can exhibit high invasion, distant metastasis, high recurrence risk, poor prognosis, LncRNA molecules are longer than 200 nucleotides in length, but lack obvious open reading frames[7,8]. Their transcripts can be transcribed by RNA polymerase II and exhibit typical mRNA-like features, such as 5′caps[9]. Growing evidence suggests the involvement of lncRNAs in important cellular processes, including epigenetic regulation[12,13], transcriptional regulation[14], and chromosome
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