Open AccessTranscription factor AP‐4 (TFAP4)‐upstream ORF coding 66 aa inhibits the malignant behaviors of glioma cells by suppressing the TFAP4/long noncoding RNA 00520/microRNA‐520f‐3p feedback loop
Author(s) -
Wang Yipeng,
Yang Chunqing,
Liu Xiaobai,
Zheng Jian,
Zhang Fangfang,
Wang Di,
Xue Yixue,
Li Xiaozhi,
Shen Shuyuan,
Shao Lianqi,
Yang Yang,
Liu Libo,
Ma Jun,
Liu Yunhui
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14308
Subject(s) - gene knockdown , biology , glioma , microrna , untranslated region , transcription (linguistics) , five prime untranslated region , three prime untranslated region , long non coding rna , transcription factor , cancer research , upstream open reading frame , non coding rna , messenger rna , rna , genetics , gene , linguistics , philosophy
Upstream ORF (uORF) is a translational initiation element located in the 5′UTR of eukaryotic mRNAs. Studies have found that uORFs play an important regulatory role in many diseases. Based on The Cancer Genome Atlas database, the results of our experiments and previous research evidence, we investigated transcription factor AP‐4 (TFAP4) and its uORF, LIM and SH3 protein 1 (LASP1), long noncoding RNA 00520 (LINC00520), and microRNA (miR)‐520f‐3p as candidates involved in glioma malignancy, which is a poorly understood process. Both TFAP4‐66aa‐uORF and miR‐520f‐3p were downregulated, and TFAP4, LASP1, and LINC00520 were highly expressed in glioma tissues and cells. TFAP4‐66aa‐uORF or miR‐520f‐3p overexpression or TFAP4, LASP1, or LINC00520 knockdown inhibited glioma cell proliferation, migration, and invasion, but promoted apoptosis. TFAP4‐66aa‐uORF inhibited the translation of TFAP4 by binding to the TFAP4 mRNA. MicroRNA‐520f‐3p inhibited TFAP4 expression by binding to its 3′UTR. However, LINC00520 could promote the expression of TFAP4 by competitively binding to miR‐520f‐3p. In addition, TFAP4 transcriptionally activated LASP1 and LINC00520 expression by binding to their promoter regions, forming a positive feedback loop of TFAP4/LINC00520/miR‐520f‐3p. Our findings together indicated that TFAP4‐66aa‐uORF inhibited the TFAP4/LINC00520/miR‐520f‐3p feedback loop by directly inhibiting TFAP4 expression, subsequently leading to inhibition of glioma malignancy. This provides a basis for developing new therapeutic approaches for glioma treatment.