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Long non-coding RNA LINC00460 promotes proliferation and inhibits apoptosis of cervical cancer cells by targeting microRNA-503-5p

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Abstract

Long non-coding RNAs are associated with the pathogenesis of cancers. Moreover, LINC00460 is involved in the development of multiple cancers. However, the function of LINC00460 in cervical cancer (CC) remains inconclusive. Herein, CC tissues and tumor-adjacent tissues were collected from patients. The effect of LINC00460 silencing in cell proliferation and apoptosis in CC was explored in vitro and in vivo. Additionally, the interaction between LINC00460 and miR-503-5p was analyzed using dual luciferase reporter assay. The expression of genes and proteins was assayed using quantitative real-time PCR, western blotting and immunohistochemistry, cell viability using MTT assay, cell cycle distribution using flow cytometry, cell apoptosis using Annexin V staining, Hoechst staining and TUNEL assay. LINC00460 levels in CC tissues were higher than tumor-adjacent tissues. LINC00460 silencing suppressed proliferation and promoted apoptosis of CC cells as evidenced by decreased cell viability, inhibited proliferation-related protein and cell cycle protein expressions and G1/S transition, increased apoptotic cells and Hoechst-positive cells, and enhanced apoptosis-related protein expressions. LINC00460 could bind to miR-503-5p and LINC00460 silencing enhanced miR-503-5p expression and inhibited its target gene expressions in CC cells. MiR-503-5p inhibition reversed LINC00460 silencing-caused inhibition of cell proliferation and miR-503-5p target gene expressions, and promotion of cell apoptosis. LINC00460 silencing also attenuated tumor growth, promoted miR-503-5p levels and cell apoptosis, and inhibited cell proliferation and miR-503-5p target gene expressions in tumor tissues. Hence, LINC00460 functioned as an oncogene in CC that affected cell proliferation and apoptosis via sponging miR-503-5p. This study provides a novel therapeutic target for CC.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Authors and Affiliations

  1. Department of Ultrasound, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, Liaoning, People’s Republic of China

    Lin Lin, Xin-lu Wang, Hua Yang & Tie-mei Shi

  2. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China

    Bing Xin & Tao Jiang

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  1. Lin Lin
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  2. Bing Xin
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  4. Xin-lu Wang
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Contributions

T.-m.S. conceived and designed the experiments. Material preparation, data collection and analysis were performed by L.L., B.X., T.J. X.-l.W. and H.Y. The first draft of the manuscript was written by L.L. and all authors commented on previous versions of the manuscript.

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Correspondence to Tie-mei Shi.

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Animal experiments were performed in accordance with National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. All experiments were approved by Ethics Committee of Shengjing Hospital of China Medical University.

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Lin, L., Xin, B., Jiang, T. et al. Long non-coding RNA LINC00460 promotes proliferation and inhibits apoptosis of cervical cancer cells by targeting microRNA-503-5p. Mol Cell Biochem 475, 1–13 (2020). https://doi.org/10.1007/s11010-020-03853-0

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