circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer
Tóm tắt
Increasing studies has found that circular RNAs (circRNAs) play vital roles in cancer progression. But the expression profile and function of circRNAs in triple-negative breast cancer (TNBC) are unclear. We used a circRNA microarray to explore the circRNA expression profile of TNBC. The expression of the top upregulated circRNA, circKIF4A, was confirmed by qRT-PCR in breast cancer cell lines and tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of circKIF4A on TNBC. A series of experiments was performed to explore the functions of circKIF4A in TNBC progression, such as cell proliferation and migration. We investigated the regulatory effect of circKIF4A on miRNA and its target genes to explore the potential regulatory mechanisms of circKIF4A in TNBC. qRT-PCR analyses verified that circKIF4A was significantly upregulated and positively associated with poorer survival of TNBC. The inhibition of circKIF4A suppressed cell proliferation and migration in TNBC. Luciferase reporter assay and RNA immunoprecipitation assay revealed that circKIF4A and KIF4A could bind to miR-375 and that circKIF4A regulated the expression of KIF4A via sponging miR-375. The circKIF4A-miR-375-KIF4A axis regulates TNBC progression via the competitive endogenous RNA (ceRNA) mechanism. circKIF4A may therefore serve as a prognostic biomarker and therapeutic target for TNBC.
Tài liệu tham khảo
citation_journal_title=Nat Biotechnol; citation_title=Detecting and characterizing circular RNAs; citation_author=WR Jeck, NE Sharpless; citation_volume=32; citation_publication_date=2014; citation_pages=453-461; citation_doi=10.1038/nbt.2890; citation_id=CR1
citation_journal_title=Nature; citation_title=The multilayered complexity of ceRNA crosstalk and competition; citation_author=Y Tay, J Rinn, PP Pandolfi; citation_volume=505; citation_publication_date=2014; citation_pages=344-352; citation_doi=10.1038/nature12986; citation_id=CR2
citation_journal_title=Trends Genet; citation_title=The emerging function and mechanism of ceRNAs in cancer; citation_author=Y Wang, J Hou, D He, M Sun, P Zhang, Y Yu, Y Chen; citation_volume=32; citation_publication_date=2016; citation_pages=211-224; citation_doi=10.1016/j.tig.2016.02.001; citation_id=CR3
citation_journal_title=Nature; citation_title=Circular RNAs are a large class of animal RNAs with regulatory potency; citation_author=S Memczak, M Jens, A Elefsinioti, F Torti, J Krueger, A Rybak, L Maier, SD Mackowiak, LH Gregersen, M Munschauer; citation_volume=495; citation_publication_date=2013; citation_pages=333-338; citation_doi=10.1038/nature11928; citation_id=CR4
citation_journal_title=Cancer Res; citation_title=Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis; citation_author=KY Hsiao, YC Lin, SK Gupta, N Chang, L Yen, HS Sun, SJ Tsai; citation_volume=77; citation_publication_date=2017; citation_pages=2339-2350; citation_doi=10.1158/0008-5472.CAN-16-1883; citation_id=CR5
citation_journal_title=Nucleic Acids Res; citation_title=Identification of senescence-associated circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1; citation_author=AC Panda, I Grammatikakis, KM Kim, S De, JL Martindale, R Munk, X Yang, K Abdelmohsen, M Gorospe; citation_volume=45; citation_publication_date=2017; citation_pages=4021-4035; citation_doi=10.1093/nar/gkw1201; citation_id=CR6
citation_journal_title=J Exp Clin Cancer Res; citation_title=circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a; citation_author=R He, P Liu, X Xie, Y Zhou, Q Liao, W Xiong, X Li, G Li, Z Zeng, H Tang; citation_volume=36; citation_publication_date=2017; citation_pages=145; citation_doi=10.1186/s13046-017-0614-1; citation_id=CR7
citation_journal_title=Cell Death Differ; citation_title=Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity; citation_author=WW Du, L Fang, W Yang, N Wu, FM Awan, Z Yang, BB Yang; citation_volume=24; citation_publication_date=2017; citation_pages=357-370; citation_doi=10.1038/cdd.2016.133; citation_id=CR8
citation_journal_title=Nucleic Acids Res; citation_title=Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2; citation_author=WW Du, W Yang, E Liu, Z Yang, P Dhaliwal, BB Yang; citation_volume=44; citation_publication_date=2016; citation_pages=2846-2858; citation_doi=10.1093/nar/gkw027; citation_id=CR9
citation_journal_title=Clin Cancer Res; citation_title=Circular RNA ciRS-7-a promising prognostic biomarker and a potential therapeutic target in colorectal cancer; citation_author=W Weng, Q Wei, S Toden, K Yoshida, T Nagasaka, T Fujiwara, S Cai, H Qin, Y Ma, A Goel; citation_volume=23; citation_publication_date=2017; citation_pages=3918-3928; citation_doi=10.1158/1078-0432.CCR-16-2541; citation_id=CR10
citation_journal_title=Nat Commun; citation_title=Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs; citation_author=Q Zheng, C Bao, W Guo, S Li, J Chen, B Chen, Y Luo, D Lyu, Y Li, G Shi; citation_volume=7; citation_publication_date=2016; citation_pages=11215; citation_doi=10.1038/ncomms11215; citation_id=CR11
citation_journal_title=Hepatology; citation_title=Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression; citation_author=D Han, J Li, H Wang, X Su, J Hou, Y Gu, C Qian, Y Lin, X Liu, M Huang; citation_volume=66; citation_publication_date=2017; citation_pages=1151-1164; citation_doi=10.1002/hep.29270; citation_id=CR12
citation_journal_title=J Hepatol; citation_title=Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma; citation_author=J Yu, QG Xu, ZG Wang, Y Yang, L Zhang, JZ Ma, SH Sun, F Yang, WP Zhou; citation_volume=68; citation_publication_date=2018; citation_pages=1214-1227; citation_doi=10.1016/j.jhep.2018.01.012; citation_id=CR13
citation_journal_title=Oncogene; citation_title=Circular RNAs in cancer: opportunities and challenges in the field; citation_author=LS Kristensen, TB Hansen, MT Veno, J Kjems; citation_volume=37; citation_publication_date=2018; citation_pages=555-565; citation_doi=10.1038/onc.2017.361; citation_id=CR14
citation_journal_title=Int J Cancer; citation_title=The emerging role of miR-375 in cancer; citation_author=JW Yan, JS Lin, XX He; citation_volume=135; citation_publication_date=2014; citation_pages=1011-1018; citation_doi=10.1002/ijc.28563; citation_id=CR15
citation_journal_title=Gut; citation_title=MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor; citation_author=KL Kong, DL Kwong, TH Chan, SY Law, L Chen, Y Li, YR Qin, XY Guan; citation_volume=61; citation_publication_date=2012; citation_pages=33-42; citation_doi=10.1136/gutjnl-2011-300178; citation_id=CR16
citation_journal_title=Cell Res; citation_title=MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2; citation_author=L Ding, Y Xu, W Zhang, Y Deng, M Si, Y Du, H Yao, X Liu, Y Ke, J Si, T Zhou; citation_volume=20; citation_publication_date=2010; citation_pages=784-793; citation_doi=10.1038/cr.2010.79; citation_id=CR17
citation_journal_title=Oncogene; citation_title=MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo; citation_author=XX He, Y Chang, FY Meng, MY Wang, QH Xie, F Tang, PY Li, YH Song, JS Lin; citation_volume=31; citation_publication_date=2012; citation_pages=3357-3369; citation_doi=10.1038/onc.2011.500; citation_id=CR18
citation_journal_title=Oncogene; citation_title=Re-expression of microRNA-375 reverses both tamoxifen resistance and accompanying EMT-like properties in breast cancer; citation_author=A Ward, A Balwierz, JD Zhang, M Kublbeck, Y Pawitan, T Hielscher, S Wiemann, O Sahin; citation_volume=32; citation_publication_date=2013; citation_pages=1173-1182; citation_doi=10.1038/onc.2012.128; citation_id=CR19
citation_journal_title=Cell Death Dis; citation_title=Upregulation of kinesin family member 4A enhanced cell proliferation via activation of Akt signaling and predicted a poor prognosis in hepatocellular carcinoma; citation_author=Y Huang, H Wang, Y Lian, X Wu, L Zhou, J Wang, M Deng, Y Huang; citation_volume=9; citation_publication_date=2018; citation_pages=141; citation_doi=10.1038/s41419-017-0114-4; citation_id=CR20
citation_journal_title=Mol Cancer Res; citation_title=Kinesin family deregulation coordinated by bromodomain protein ANCCA and histone methyltransferase MLL for breast cancer cell growth, survival, and tamoxifen resistance; citation_author=JX Zou, Z Duan, J Wang, A Sokolov, J Xu, CZ Chen, JJ Li, HW Chen; citation_volume=12; citation_publication_date=2014; citation_pages=539-549; citation_doi=10.1158/1541-7786.MCR-13-0459; citation_id=CR21
citation_journal_title=Clin Cancer Res; citation_title=Activation of KIF4A as a prognostic biomarker and therapeutic target for lung cancer; citation_author=M Taniwaki, A Takano, N Ishikawa, W Yasui, K Inai, H Nishimura, E Tsuchiya, N Kohno, Y Nakamura, Y Daigo; citation_volume=13; citation_publication_date=2007; citation_pages=6624-6631; citation_doi=10.1158/1078-0432.CCR-07-1328; citation_id=CR22