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Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3–c-Myc axis

Abstract

Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in cancer long noncoding RNAs (lncRNAs) have been known to play crucial roles in cancer development and progression by regulating chromatin dynamics and gene expression. However, only a few lncRNAs with annotated functions in the progression of colorectal cancer (CRC) have been identified to date. In the present study, the expression of lncCMPK2 was upregulated in CRC tissues and positively correlated with clinical stages and lymphatic metastasis. The overexpression of lncCMPK2 promoted the proliferation and cell cycle transition of CRC cells. Conversely, the silencing of lncCMPK2 restricted cell proliferation both in vitro and in vivo. lncCMPK2 was localized to the nucleus of CRC cells, bound to far upstream element binding protein 3 (FUBP3), and guided FUBP3 to the far upstream element (FUSE) of the c-Myc gene to activate transcription. lncCMPK2 also stabilized FUBP3. These results provide novel insights into the functional mechanism of lncCMPK2 in CRC progression and highlight its potential as a biomarker of advanced CRC and therapeutic target.

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Fig. 1: LncCMPK2 is overexpressed in CRC tissues and cells.
Fig. 2: Overexpression of lncCMPK2 promotes CRC cells proliferation.
Fig. 3: Silencing of lncCMPK2 inhibits the proliferation of CRC.
Fig. 4: LncCMPK2 increases the stability of FUBP3 through interaction.
Fig. 5: LncCMPK2 increases the c-Myc expression via FUBP3 and promote CRC cell proliferation.
Fig. 6: The positive correlation among lncCMPK2, FUBP3, and c-Myc expression in CRC tissues.

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Data availability

Data and material are available in Supplementary Data.

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Acknowledgements

We would like to thank Editage [www.editage.cn] and BioMed Proofreading@ LLC [www.biomedproofreading.com] for English language editing.

Funding

This work was supported by the National Natural Science Foundation of China (nos. 81572813, 81773082, 81702903, and 81872423), Guangdong Natural Science Foundation (2016A030313626, 2017A030310038, 2018B030311036), and Fork Ying Tung Education Foundation (161035).

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LZ led the study design and prepared the paper. Q-ZG and RZ carried out the experiments. YM and R-FD performed statistical analysis; LW and RL assisted in tissue sample collection. F-LD performed data analysis and interpretation. CL collected the data.

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Correspondence to Liang Zhao.

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All experiments performed are endorsed by the Ethics Committee of Southern Medical University and complied with the Declaration of Helsinki. All animal experiments were carried out with the approval of the Southern Medical University Animal Care and Use Committee in accordance with the guidelines for the ethical treatment of animals. All animal experiments involved ethical and humane treatment under a license from the Guangdong Provincial Bureau of Science.

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Gao, Q., Zhou, R., Meng, Y. et al. Long noncoding RNA CMPK2 promotes colorectal cancer progression by activating the FUBP3–c-Myc axis. Oncogene 39, 3926–3938 (2020). https://doi.org/10.1038/s41388-020-1266-8

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