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lncRNA GAS5‐promoted apoptosis in triple‐negative breast cancer by targeting miR‐378a‐5p/SUFU signaling
Author(s) -
Zheng Shipeng,
Li Mengquan,
Miao Keke,
Xu Han
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29445
Subject(s) - gas5 , apoptosis , cancer research , triple negative breast cancer , flow cytometry , triptolide , cell growth , long non coding rna , biology , chemistry , downregulation and upregulation , cancer , microbiology and biotechnology , breast cancer , gene , biochemistry , genetics
Purpose Long‐chain noncoding RNAs (lncRNAs) are involved in regulating the sensitivity of cancer cells to chemotherapeutic drugs, but the specific mechanism of action is not well understood. The aim of this study was to investigate the effect of lncRNA growth‐stasis specific transcript 5 (GAS5) on triple‐negative breast cancer (TNBC). Methods Quantitative real‐time polymerase chain reaction and flow cytometry were used to screen lncRNA associated with tumor resistance. Double luciferase reporter gene assay, flow cytometry, and Western blot assay were used to determine whether miRNA 378a‐5p and SUFU were involved in tumor cell apoptosis induced by lncRNA GAS5. A mouse model of subcutaneous xenografts was established to investigate the relationship between lncRNA GAS5 and tumor resistance in vivo. Results In this study, the expression of lncRNA GAS5 was significantly downregulated in cells treated with paclitaxel (PTX) or cisplatin (CIS). Furthermore, TNBC cells with low expression of lncRNA GAS5 had a lower percentage of apoptosis under stress conditions, especially in serum‐free medium. More interestingly, the expression level of lncRNA GAS5 in TNBC patients was associated with tumor resistance to PTX and CIS. In addition, RNA immunoprecipitation experiments confirmed that lncRNA GAS5 and miR‐378 could directly bind to each other. Moreover, the miR‐378a‐5p target of SUFU could promote lncRNA GAS5‐induced apoptosis of TNBC cells. Finally, lncRNA GAS5 overexpressed MDA‐231R could enhance the sensitivity of TNBC to PTX. Conclusion The above results confirmed that lncRNA GAS5 could induce apoptosis in TNBC cells by targeting miR‐378a‐5p/SUFU signaling.