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SP1-induced overexpression of LINC00520 facilitates non-small cell lung cancer progression through miR-577/CCNE2 pathway and predicts poor prognosis

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Abstract

Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. Long intergenic non-protein coding RNA 520 (LINC00520) was one of the newly discovered lncRNA which has been demonstrated to be dysregulated in several cancers. So far, the function and mechanism of LINC00520 in non-small cell lung cancer (NSCLC) are unclear. In this paper, our group first showed that LINC00520 level was elevated in non-small cell lung cancer (NSCLC) tissue and cells. In addition, SP1 could bind directly to the promoter region of LINC00520 and thus promote its transcription. Increased LINC00520 was distinctly correlated with advanced tumor stage and shorter survival time in NSCLC patients. Further functional investigations provided evidences that forced down regulation of LINC00520 inhibited NSCLC cell proliferation, invasion, metastasis and EMT, while contributing to cells apoptosis. Mechanistically, we found that LINC00520 serving as a competing endogenous RNA to be involved in the modulation of miR-577 expressions, and thus affected the expression of CCNE2 which was a target gene of miR-577. Moreover, in NSCLC cells with si-LINC00520, up regulation of CCNE2 led to an increase of cell growth and invasion. Taken together, LINC00520 displayed its tumor-promotive roles through modulating the miR-577/CCNE2 axis, highlighting a potential therapeutic strategy for NSCLC patients.

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Funding

This work was supported by Henan Provincial Chest Hospital for Scientific Research (No. 2018-0147).

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Authors and Affiliations

  1. Department of Respiration Ward II, Henan Provincial Chest Hospital, Weiwu Road No. 1, Zhengzhou, Henan, China

    Ji-fang Wang, Zhuo-na Xi, Hong-jian Su, Zhen Bao & Ya-hong Qiao

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  1. Ji-fang Wang
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  2. Zhuo-na Xi
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  3. Hong-jian Su
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Contributions

J-fW and Y-hQ conceived and designed the experiments, J-fW, Z-nX and ZB analyzed, and interpreted the results of the experiments, J-fW, Z-nX and H-jS performed the experiments.

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Correspondence to Ya-hong Qiao.

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Wang, Jf., Xi, Zn., Su, Hj. et al. SP1-induced overexpression of LINC00520 facilitates non-small cell lung cancer progression through miR-577/CCNE2 pathway and predicts poor prognosis. Human Cell 34, 952–964 (2021). https://doi.org/10.1007/s13577-021-00518-y

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