Long non‑coding RNA DANCR aggravates breast cancer through the miR‑34c/E2F1 feedback loop

Abstract

Emerging scientific evidence has suggested that the long non-coding (lnc)RNA differentiation antagonizing non-protein coding RNA ( DANCR ) serves a significant role in human tumorigenesis and cancer progression; however, the precise mechanism of its function in breast cancer remains to be fully understood. Therefore, the objective of the present study was to manipulate DANCR expression in MCF7 and MDA-MB-231 cells using lentiviral vectors to knock down or overexpress DANCR . This manipulation, alongside the analysis of bioinformatics data, was performed to investigate the potential mechanism underlying the role of DANCR in cancer. The mRNA and/or protein expression levels of DANCR, miR-34c-5p and E2F transcription factor 1 ( E2F1 ) were assessed using reverse transcription-quantitative PCR and western blotting, respectively. The interactions between these molecules were validated using chromatin immunoprecipitation and dual-luciferase reporter assays. Additionally, fluorescence in situ hybridization was used to confirm the subcellular localization of DANCR . Cell proliferation, migration and invasion were determined using 5-ethynyl-2′-deoxyuridine, wound healing and Transwell assays, respectively. The results of the present study demonstrated that DANCR had a regulatory role as a competing endogenous RNA and upregulated the expression of E2F1 by sequestering miR-34c-5p in breast cancer cells. Furthermore, E2F1 promoted DANCR transcription by binding to its promoter in breast cancer cells. Notably, the DANCR / miR-34c-5p / E2F1 feedback loop enhanced cell proliferation, migration and invasion in breast cancer cells. Thus, these findings suggested that targeting DANCR may potentially provide a promising future therapeutic strategy for breast cancer treatment.

The functions and mechanisms of long non-coding RNA in colorectal cancer

“…lncRNAs can be located in the cytoplasm ( 28 ), nucleus ( 29 ), nucleolus ( 30 )s, and other subcellular regions and vesicles (such as nucleoli and exosomes), and their localization is related to their molecular functions ( 28 , 31 ). Certain sequence motifs in their primary sequences are related to subcellular localization ( 32 ).…”

Activation of lncRNA DANCR by H3K27 acetylation regulates proliferation of colorectal cancer cells

“…It has also been reported that roles of DANCR in the carcinogenesis, with an especial emphasis on its role in the development of osteosarcoma and lung, liver, pancreatic and CRC [ 11 ]. Study also showed DANCR may potentially provide a promising future therapeutic strategy for breast cancer treatment [ 12 ]. Previous research has reported that DANCR played a critical role in Doxorubicin-induced apoptosis in colorectal cancer cells through regulating the expression of MALAT1 [ 13 ].…”