Abstract
BackgroundBreast cancer (BC) is one of the malignant solid tumors with the highest morbidity in the world. Currently, the therapeutic outcome of different types of treatment can be unsatisfactory. Novel lncRNA biomarkers in BC remains to be further explored.MethodsDifferent expression of lncRNAs among BC tissues and adjacent normal tissues were identified with microarray analyses. A series of in vivo and in vitro gain-of-function laboratory procedures were conducted to study the biological functions of IGBP1-AS1. The prognostic effects on IGBP1-AS1 survival were evaluated by using in situ hybridization and survival analysis. In addition, other experiments including RNA pull down analysis, RNA immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation as well as validating assays conducted in vivo were applied to identify the target and regulatory mechanisms of IGBP1-AS1.ResultsSignificant down-regulation of IGBP1-AS1 was discovered in the cell lines and tissues of BC. With respect to its biological function, overexpression of IGBP1-AS1 had inhibitory effects on the invasion and proliferation of BC cells in vivo as well as in vitro. Analysis of the samples obtained from BC patients indicated a positive effect of IGBP1-AS1 on survival outcomes. LncRNA IGBP1-AS1/miR-24-1/ZIC3 axis as a loop can regulate the proliferation and invasion of BC cells.ConclusionsIGBP1-AS1 could have inhibitory impact on the invasion and proliferation of BC and may serve as a promising biomarker for BC.
Highlights
Breast cancer (BC) is one of the malignant solid tumors with the highest morbidity in the world
We found that miR-24-1 may be sponged by IGBP1-AS1. miR-24-1 has been reported to be involved in tumorigenesis or chemoprevention of colorectal cancer, ovarian cancer, pediatric pilocytic astrocytomas and ependymomas [9,10,11]
Cell apoptosis was analyzed with the Annexin V-FITC early apoptosis kit, and the flow cytometer (FACScan; BD Biosciences) was adopted to analyze the IGBP1-AS1overexpressed BC cells and negative control cells, the results of which was calculated by CellQuest software (BD Biosciences)
Summary
Breast cancer (BC) is one of the malignant solid tumors with the highest morbidity in the world. Treatment for BC includes surgery, chemotherapy, radiotherapy, endocrine therapy and targeted therapy the therapeutic effect often remains unsatisfactory. RNAs that cannot encode proteins are considered useless RNAs or transcriptional noise These RNAs play an indispensable role in important activities such as cell proliferation, Chen et al Cancer Cell Int (2020) 20:153 differentiation, senescence and apoptosis. Ponting et al [6] studied the evolution of lncRNAs and their role in transcriptional regulation and epigenetic gene regulation They speculated that lncRNAs may have five different origins: generated by (1) protein-coding gene sequence disruption; (2) chromatin rearrangement; (3) noncoding RNA reverse transcriptional translocation; (4) noncoding genes containing adjacent repeats; and (5) insertion of a transposable element into the genome. The biological functions of lncRNA are mainly accomplished through signaling molecules, decoy molecules, guide molecules, scaffold molecules and chromatin modification complexes, occurring at both the transcriptional level and the posttranscriptional level, and by structural RNAs in cell proliferation, differentiation, senescence, death, carcinogenesis, and the occurrence and development of disease [7]
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