Long non-coding RNA ARHGAP5-AS1 inhibits the proliferation, migration andinvasion of breast cancer cells
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Abstract:
Objective: To detect the expression of long non-coding RNA (lncRNA) ARHGAP5-AS1 in breast cancer (BC) tissues and cell lines, analyze its relationship with the clinicopathological parameters and prognosis of BC patients, and to investigate its effect on the proliferation, migration and invasion of BC cells in vitro. Methods: LncRNA ARHGAP5-AS1 that low expressed in BC and associated with poor prognosis was screened out by bioinformatics analysis of BC-related data sets in TCGA database. qPCR was used to verify the expression of lncRNA ARHGAP5-AS1 in BC tissues collected from April 2010 to October 2016 in the Department of Oncology, Affiliated Hospital of Jiangnan University. χ2 test was used to analyze the relationship between the expression of ARHGAP5-AS1 and the clinicopathological parameters of BC patients. Kaplan-Meier survival analysis was performed to construct a survival curve to compare the overall and recurrence-free survival of the high and low expression groups. The effects of ARHGAP5-AS1 knockdown on the proliferation, migration and invasion of MDA-MB-231 and BT-549 cells were examined by CCK-8, Wound-healing assay and Transwell assay. Results: TCGA database analysis showed that the expression level of ARHGAP5-AS1 in BC tissues was significantly lower than that in normal breast tissues (P<0.01), and its low expression was significantly related to larger tumor diameter (T3), distant metastasis (M1), negative ER and PR, and shorter overall survival (all P<0.05). ARHGAP5-AS1 expression was significantly down-regulated in BC tissues compared with adjacent specimens (P<0.05), which was significantly associated with larger tumor diameter and lymph node metastasis (all P<0.05) in BC patients. Furthermore, ARHGAP5-AS1 was also reduced in 6 BC cell lines (MDA-MB-231, BT-549, MDA-MB-468, MCF-7, HCC1937, Hs578T) compared with normal breast epithelial cell line MCF-10A (all P<0.05). Cell function experiments showed that ARHGAP5-AS1 knockdown promoted proliferation, migration and invasion of MDA-MB-231 and BT-549 cells (all P<0.05). Conclusion: The abnormally low expression of ARHGAP5-AS1 may affect the occurrence and development of breast cancer by promoting the proliferation, migration and invasion of breast cancer cells.
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Project supported by the Science and Technology Development Foundation of Wuxi City (No.20192029)