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DLGAP1-AS2 promotes human colorectal cancer progression through trans-activation of Myc

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Abstract

Substantial evidence suggests that non-coding RNA plays a vital role in human cancer, especially long non-coding RNA (lncRNA) with a length greater than 200nt. Herein, we found a lncRNA facilitating human colorectal cancer (CRC) progression. DLGAP1-AS2 was significantly increased in CRC tissues and cell lines. Knockdown of DLGAP1-AS2 inhibited CRC cell proliferation, migration, invasion in vitro, and tumor growth in vivo. The subcellular localization of DLGAP1-AS2 was translocated from the cytoplasm of normal cells to the nucleus of CRC cells due to reduced levels of N6-methyladenosine (m6A) modification. Further, through the screening of a series of signal pathways, we found that Myc pathway was involved in the effect of DLGAP1-AS2. Silencing of DLGAP1-AS2 markedly reduced Myc mRNA and protein levels. Blockade of Myc effectively abolished the enhanced aggressive behaviors of CRC cells caused by DLGAP1-AS2 overexpression. Mechanistically, DLGAP1-AS2 directly bound CTCF, a well-known transcriptional repressor of Myc, resulting in reduced binding of CTCF on Myc promoter and activating Myc transcription. The second hairpin structure of DLGAP1-AS2 was critical for the interaction between DLGAP1-AS2 and CTCF in the nucleus. Taken together, our study reveals the oncogenic regulatory axis of DLGAP1-AS2/CTCF/Myc in CRC, implying a promising targeted therapy for clinical application.

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The data in this study are available from the corresponding author upon request.

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Authors and Affiliations

  1. Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Dong Road, Erqi District, Zhengzhou, 450003, People’s Republic of China

    Chunfeng Ren, Jingjing Pan, Qian Chang, Wanhai Wang, Xiaobing Guo & Jing Bian

  2. Department of General Surgery, Luoyang Central People’s Hospital, Luoyang, 471000, People’s Republic of China

    Hongbin Han

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  1. Chunfeng Ren
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  2. Hongbin Han
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  3. Jingjing Pan
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  4. Qian Chang
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  5. Wanhai Wang
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  6. Xiaobing Guo
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  7. Jing Bian
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Contributions

CFR: designed this study and wrote the draft; HBH, JJP, and QC: performed all experiments and collected data; CFR, WHW, XBG, and JB: provided technical assistance and guidance. All authors approved the final version.

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Correspondence to Chunfeng Ren.

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The authors declare that they have no financial conflicts of interest.

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This study was approved by the Medical Ethics Committee and Institutional Animal Care and Use Committee (IACUC) of the First Affiliated Hospital of Zhengzhou University.

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Ren, C., Han, H., Pan, J. et al. DLGAP1-AS2 promotes human colorectal cancer progression through trans-activation of Myc. Mamm Genome 33, 672–683 (2022). https://doi.org/10.1007/s00335-022-09963-y

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  • DOI: https://doi.org/10.1007/s00335-022-09963-y

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