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LINC00467 is up-regulated by TDG-mediated acetylation in non-small cell lung cancer and promotes tumor progression

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Abstract

The long non-coding RNA (LncRNA) abnormally expresses in several cancers including non-small cell lung cancer (NSCLC). To better understand the role of key lncRNA involving cancer progress, we conduct a comprehensive data mining on LINC00467 and determine its molecular mechanisms. We identified LINC00467 was the up-regulated lncRNA that common significantly differentially expressed in NSCLC and CRC tissues from GEO database. LINC00467 highly expressed in NSCLC tissues and associated with advanced clinical stages and poor outcome. Knockdown of LINC00467 inhibited cell growth and metastasis via regulating the Akt signaling pathway. Finally, we demonstrated that TDG mediated acetylation is the key factor controlling LINC00467 expression. In conclusion, LINC00467 promotes NSCLC progression via Akt signal pathway. The identified LINC00467 may serve as a valuable diagnostic and prognostic biomarker as well as a therapeutic target for NSCLC.

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Fig. 1: LINC00467 plays a pivotal role in NSCLC.
Fig. 2: LINC00467 promotes metastasis in NSCLC.
Fig. 3: LINC00467 activates AKT, can bind and promote the degradation of AZGP1.
Fig. 4: Knockdown of AZGP1 up-regulates p-AKT and promotes cell migration and invasion.
Fig. 5: LINC00467 up-regulated by TDG mediated acetylation.
Fig. 6: Knockdown of TDG-mediated histone acetylation contributes to inhibit tumor progress.
Fig. 7: TDG promotes tumor development of NSCLC.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgement

We thank all the authors for their excellent work.

Funding

This work was supported by the National Natural Science Foundation of China (81874137), the Outstanding Youth Foundation of Hunan Province (2018JJ1047), the Huxiang Young Talent Project (2016RS3022). the Hunan Province Science and technology talent promotion project (2019TJ-Q10), the Project of scientific research plan of health and Family Planning Commission of Hunan Province (c20180476).

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  1. These authors contributed equally: Yuxing Zhu, Jingjing Li, Hao Bo

Authors and Affiliations

  1. Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, 410013, China

    Yuxing Zhu, Jingjing Li, Mengqing Xiao, Liang Xiang, Lian Gong, Yi Hu, Yeyu Zhang, Yaxin Cheng, Liping Deng, Rongrong Zhu, Yanni Ma & Ke Cao

  2. Department of Plastic Surgery, Xiangya Hospital of Central South University, Changsha, 410008, China

    Jingjing Li

  3. Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410078, China

    Hao Bo

  4. Key Laboratory of Reproductive and Stem Cell Engineering, National Health and Family Planning Commission, Institute of Reproductive and Stem Cell Engineering, Basic Medicine College, Central South University, Changsha, 410078, China

    Hao Bo

  5. Department of Respiratory, The Second People’s Hospital of Hunan Province, Chansha, 410007, China

    Dong He

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  1. Yuxing Zhu
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Contributions

KC designed the study, YXZ, JJL analyzed and interpreted the data, and wrote the manuscript. HB completed all the bio-analysis of this article study. DH, MQX, LX, LG, and YH contributed to data acquisition, analysis and interpretation. YYZ provided clinical database compilation and analysis. YXC performed all bioinformatics analysis. LPD, RRZ, and YNM carried out the experiments. All authors have seen and approved the final version of the manuscript.

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Correspondence to Ke Cao.

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The research was approved by the Ethics Committee of Third Xiangya Hospital of Central South University.

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Zhu, Y., Li, J., Bo, H. et al. LINC00467 is up-regulated by TDG-mediated acetylation in non-small cell lung cancer and promotes tumor progression. Oncogene 39, 6071–6084 (2020). https://doi.org/10.1038/s41388-020-01421-w

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